Drug Details

General Information of the Drug (ID: DR8680)
Name
TNF-related apoptosis inducing ligand
Disease Lung cancer [ICD-11: 2C25] Phase 3 [1]
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GDSC
TRAIL
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          6-dehydrogingerdione      Zingiber officinale     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 In addition to the mitochondrial- and Fas receptor-mediated apoptotic pathways involved, ROS-dependent and p53-regulated DR5 expression was also demonstrated to play a pivotal role in the synergistic enhancement of TRAIL-induced apoptosis instigated by 6-DG in Hep G2 cells.
          Apicidin      Fusarium sp.     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combination of apicidin and TRAIL may be an effective strategy for treating TRAIL-resistant Bcr-Abl expressing CML cells.
          Apigenin      Psilotum nudum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Apigenin markedly augmented TRAIL-mediated apoptosis in prostate cancer cells .
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model ML1 CVCL_0436 Adult acute myeloid leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
Raji CVCL_0511 EBV-related Burkitt lymphoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
COLO 205 CVCL_0218 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 TRAIL sensitisation by arsenic trioxide is caspase-8 dependent and involves modulation of death receptor components and Akt.
          Betulinic Acid      Rubus alceifolius     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
                    In-vivo Model 5*105 HUH7 cells were subcutaneously injected into the dorsal flanks of 30 male 6-week old Athymic nude mice.
                    Experimental
                    Result(s)		 Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation.
          Bufalin      Bufo gargarizans     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CBLB  Molecule Info 
Pathway MAP
Up-regulation Expression ERK1  Molecule Info 
Pathway MAP
Up-regulation Expression JNK1  Molecule Info 
Pathway MAP
Up-regulation Expression p38 beta  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells.
          Capsaicin      Capsicum annuum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression POLD1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-343MG CVCL_S471 Glioblastoma Homo sapiens
T98 CVCL_B368 Glioblastoma Homo sapiens
SNU-444 CVCL_5060 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation.
          Carnosic acid      Salvia rosmarinus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Caki-1 CVCL_0234 Clear cell renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c-FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up-regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells.
          Celastrol      Celastrus strigillosus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
HCC15 CVCL_2057 Lung squamous cell carcinoma Homo sapiens
Calu-3 CVCL_0609 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL-induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species.
          Chrysin      Tripterygium wilfordii     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Chrysin can enhance the apoptosis induced by TRAIL, and the apoptosis is caspase-dependent and related to the activation of caspase 8.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1B  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Activity p105  Molecule Info 
Pathway MAP
Down-regulation Expression PRAP1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vivo Model LNCaP cells (2*106 cells as a 50% suspension in matrigel) in a final volume of 0.1 mL were injected subcutaneously at right flank of Balb c nude mice.
                    Experimental
                    Result(s)		 Curcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL via regulation of death receptors and members of Bcl-2 family and inactivation of NFkappaB.
          Delphinidin      Aristotelia chilensis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage.
          Elemene      Pogostemon cablin     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression FADD  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model BGC-823 CVCL_3360 Gastric cancer Homo sapiens
SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
                    Experimental
                    Result(s)		 Beta-elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts.
          Epigallocatechin gallate      Hamamelis virginiana     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PEA15  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
A-172 CVCL_0131 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma.
          Esculetin      Fraxinus chinensis     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model SAS CVCL_1675 Tongue squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Esculetin enhances TRAIL-induced apoptosis primarily through upregulation of DR5.
          Evodiamine      Evodia rutaecarpa Bentham     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CTNNB1  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Evodiamine sensitizes U87 glioblastoma cells to TRAIL via the death receptor pathway.
          Flavopiridol      Dysoxylum binectariferum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Death-inducing signaling complex (DISC) formation
Up-regulation Cytochrome c release
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
Evsa-T CVCL_1207 Breast carcinoma Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Flavopiridol sensitizes breast cancer cells to TRAIL-induced apoptosis by facilitating early events in the apoptotic pathway.
          Fucoxanthin      Saccharina japonica     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
SiHa CVCL_0032 Cervical squamous cell carcinoma Homo sapiens
Ca Ski CVCL_1100 Cervical squamous cell carcinoma Homo sapiens
                    In-vivo Model Five-week-old nude BALB/c mice were used for subcutaneous implantation of human cervical tumor cells HeLa (2*106 per site).
                    Experimental
                    Result(s)		 The combination of TRAIL with fucoxanthin showed synergistically inhibitory effects on cervical cancer cells.
          Galangin      Plantago major     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model Caki-1 CVCL_0234 Clear cell renal cell carcinoma Homo sapiens
ACHN CVCL_1067 Papillary renal cell carcinoma Homo sapiens
A-498 CVCL_1056 Renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Galangin sensitizes TRAIL-induced apoptosis through down-regulation of anti-apoptotic proteins in renal carcinoma Caki cells.
          Gambogic acid      Garcinia morella     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression BID  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux.
          Gingerol      Zingiber officinale     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death.
          Kaempferol      Equisetum hyemale     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis.
          Liquiritin      Glycyrrhiza uralensis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Apoptosis
Induction ROS generation
                    In-vitro Model AGS CVCL_0139 Gastric adenocarcinoma Homo sapiens
SNU-216 CVCL_3946 Gastric tubular adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 In combination, the two drugs functioned synergistically to impede the progression and growth of human gastric cancer cells in vitro and gastric cancer cell xenograft nude mice in vivo.
          Luteolin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model A549 non-small cell lung cancer cells (2*106) resuspended in 0.1mL of PBS were injected subcutaneously into athymic (nu/nu) male nude mice (5-6 weeks old).
                    Experimental
                    Result(s)		 Luteolin enhances TNF-related apoptosis-inducing ligand's anticancer activity in a lung cancer xenograft mouse model.
          Magnolol      Magnolia officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Caki Clear cell renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Magnolol enhanced TRAIL-induced apoptosis via ATF4-dependent DR5 upregulation and downregulation of c-FLIP and Mcl-1 proteins.
          Neferine      Nelumbo nucifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Neferine treatment effectively promotes TRAIL-mediated cell death and this effect likely occurs via the autophagic flux and the JNK pathway.
          Osthole      Angelica pubescens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model Caki Clear cell renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells.
          Paclitaxel      Taxus brevifolia     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 PX can sensitize U87 cells and U87-SLCs to TRAIL treatment through an extrinsic pathway of cell apoptosis.
          Periplocin      Periploca forrestii     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Activity CTNNB1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CTNNB1  Molecule Info 
Pathway MAP
Down-regulation Activity FOXP3  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Eca-109 CVCL_6898 Esophageal squamous cell carcinoma Homo sapiens
TE-1 CVCL_1759 Esophageal squamous cell carcinoma Homo sapiens
YES-2 CVCL_E322 Esophageal squamous cell carcinoma Homo sapiens
KYSE-30 CVCL_1351 Esophageal squamous cell carcinoma Homo sapiens
KYSE-410 CVCL_1352 Esophageal squamous cell carcinoma Homo sapiens
KYSE-510 CVCL_1354 Esophageal squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy.
          Phytosphingosine      Patiria pectinifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Phytosphingosine sensitizes cancer cells to TRAIL through the synergistic up-regulation of DR4 and DR5 in an NF-kappaB-dependent fashion resulting in caspase-8 activation and subsequent mitochondrial dysfunction.
          Piperine      Piper nigrum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation RELA  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
4T1 CVCL_0125 Malignant neoplasms Mus musculus
                    In-vivo Model 1*105 4T1-luc murine cells were inoculated directly into the mouse mammary fat pad.
                    Experimental
                    Result(s)		 Piperine enhances TRAIL-based therapeutics for TNBC.
          Pterostilbene      Vitis vinifera     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Activity DDIT3  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model BT-20 CVCL_0178 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
SK-OV-3 CVCL_0532 Ovarian serous cystadenocarcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Pterostilbene enhances TRAIL-induced apoptosis through the induction of death receptors and downregulation of cell survival proteins in TRAIL-resistance triple negative breast cancer cells.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p105  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
HCC15 CVCL_2057 Lung squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-kappaB signaling.
          Rottlerin      Mallotus philippinensis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [36]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
A-172 CVCL_0131 Glioblastoma Homo sapiens
T98 CVCL_B368 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP.
          Shikonin      Lithospermum erythrorhizon     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Down-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CASP8  Molecule Info 
Pathway MAP
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways.
          Silibinin      Carduus marianus     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [38]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC3  Molecule Info 
Pathway MAP
Up-regulation Expression PSG1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Silibinin sensitizes TRAIL-mediated apoptosis by upregulating DR5 through ROS-induced endoplasmic reticulum stress-Ca 2+-CaMKII-Sp1 pathway.
          Sulforaphane      Brassica oleracea     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [39]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Down-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK1  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
LNCaP CVCL_0395 Prostate carcinoma Homo sapiens
                    In-vivo Model Mice were inoculated with PC-3 cells (1*106 per 100 AL medium) into the dorsolateral lobe of the prostatic capsule.
                    Experimental
                    Result(s)		 Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis.
          Triptolide      Tripterygium hypoglaucum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [40]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression HSPA4  Molecule Info 
Pathway MAP
                    In-vitro Model ACHN CVCL_1067 Papillary renal cell carcinoma Homo sapiens
A-498 CVCL_1056 Renal cell carcinoma Homo sapiens
Caki-1 CVCL_0234 Clear cell renal cell carcinoma Homo sapiens
769-P CVCL_1050 Renal cell carcinoma Homo sapiens
786-O CVCL_1051 Renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Triptolide sensitizes RCC cells to TRAIL-induced apoptosis through altered TRAIL death receptor and heat shock protein expression.
          Vernodalol      Chrysanthemum x morifolium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [41]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model SU-DHL-2 CVCL_9550 B-cell lymphoma Homo sapiens
OCI-Ly8 CVCL_8803 Diffuse large B-cell lymphoma Homo sapiens
SU-DHL-4 CVCL_0539 B-cell lymphoma Homo sapiens
                    In-vivo Model Tumours were induced by injecting 5*106 cells into the right side of each nude mouse.
                    Experimental
                    Result(s)		 Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells.
          Wogonin      Scutellaria amoena     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [42]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Down-regulation Expression MAGT1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model A549 non-small-cell lung cancer cells (2*106) resuspended in 0.1mL of PBS were injected subcutaneously into six weeks old athymic (nu/nu) male nude mice.
                    Experimental
                    Result(s)		 Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Morusin      Morus australis     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [43]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-18 CVCL_0392 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Morusin induces TRAIL sensitization by regulating EGFR and DR5 in human glioblastoma cells.
    γ. A List of Natural Product(s) Able to Reverse the Resistance of This Drug
          6-shogaol      Acacia confusa     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [44]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
Caco-2 CVCL_0025 Colon adenocarcinoma Homo sapiens
SW620 CVCL_0547 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Shogaol overcomes TRAIL resistance in colon cancer cells via inhibiting of survivin.
          Curcumol      Halicephalobus sp. hali_val     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [45]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression NQO2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
NCI-H358 CVCL_1559 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
                    In-vivo Model BALB/c nude mice (5-week-old) were subcutaneously inoculated with A549 cells (1*106).
                    Experimental
                    Result(s)		 Curcumol overcomes TRAIL resistance of non-small cell lung cancer by targeting NRH:Quinone Oxidoreductase 2 (NQO2).
          Cyclopamine      Veratrum californicum     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [46]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    Experimental
                    Result(s)		 Cyclopamine sensitizes TRAIL-resistant gastric cancer cells to TRAIL-induced apoptosis via endoplasmic reticulum stress-mediated increase of death receptor 5 and survivin degradation.
          Daidzein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [47]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model NCH89 CVCL_S823 Glioblastoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
                    Experimental
                    Result(s)		 Daidzein overcomes TRAIL-resistance in malignant glioma cells by modulating the expression of the intrinsic apoptotic inhibitor, bcl-2.
          Isoliquiritigenin      Robinia pseudoacacia     Click to Show/Hide the Molecular Data of This NP
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [48]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Isoliquiritigenin has the potential to overcome resistance to TRAIL in cancer cells and its chemopreventive effects may depend on TRAIL function.
Target and Pathway
Target(s) Aurora kinase A (AURKA)  Molecule Info  [49]
Aurora kinase B (AURKB)  Molecule Info  [49]
Aurora kinase C (AURKC)  Molecule Info  [49]
KEGG Pathway Oocyte meiosis Click to Show/Hide
Pathway Interaction Database Aurora B signaling Click to Show/Hide
2 Signaling by Aurora kinases
3 Integrin-linked kinase signaling
4 PLK1 signaling events
5 Aurora A signaling
6 Aurora C signaling
7 FOXM1 transcription factor network
Reactome APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 Click to Show/Hide
2 Regulation of PLK1 Activity at G2/M Transition
3 Separation of Sister Chromatids
4 Resolution of Sister Chromatid Cohesion
5 RHO GTPases Activate Formins
6 Mitotic Prometaphase
WikiPathways EGF/EGFR Signaling Pathway Click to Show/Hide
2 JAK/STAT
3 Gastric Cancer Network 1
4 Integrated Breast Cancer Pathway
5 APC/C-mediated degradation of cell cycle proteins
6 Mitotic Metaphase and Anaphase
7 Mitotic Prometaphase
8 Regulation of Microtubule Cytoskeleton
9 miR-targeted genes in lymphocytes - TarBase
10 miR-targeted genes in epithelium - TarBase
References
Reference 1 ClinicalTrials.gov (NCT03083743) A Phase III Trial of Recombinant Human Apo-2 Ligand for Injection
Reference 2 6-dehydrogingerdione sensitizes human hepatoblastoma Hep G2 cells to TRAIL-induced apoptosis via reactive oxygen species-mediated increase of DR5. J Agric Food Chem. 2010 May 12;58(9):5604-11.
Reference 3 Cotreatment with apicidin overcomes TRAIL resistance via inhibition of Bcr-Abl signaling pathway in K562 leukemia cells. Exp Cell Res. 2009 Jul 1;315(11):1809-18.
Reference 4 Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells. Evid Based Complement Alternat Med. 2011;2011:535172.
Reference 5 TRAIL sensitisation by arsenic trioxide is caspase-8 dependent and involves modulation of death receptor components and Akt. Br J Cancer. 2006 Feb 13;94(3):398-406.
Reference 6 Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation. Biomed Pharmacother. 2017 Apr;88:349-358.
Reference 7 Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89.
Reference 8 Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation. Carcinogenesis. 2010 Mar;31(3):367-75.
Reference 9 Carnosic acid sensitized TRAIL-mediated apoptosis through down-regulation of c-FLIP and Bcl-2 expression at the post translational levels and CHOP-dependent up-regulation of DR5, Bim, and PUMA expression in human carcinoma caki cells. Oncotarget. 2015 Jan 30;6(3):1556-68.
Reference 10 Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL?induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species. Mol Med Rep. 2019 Feb;19(2):984-993.
Reference 11 Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human cancer cell lines. Toxicol In Vitro. 2011 Apr;25(3):630-5.
Reference 12 Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer. 2008 Jan 29;7:16.
Reference 13 Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage. Oncotarget. 2015 Apr 30;6(12):9970-84.
Reference 14 Beta-elemene increases the sensitivity of gastric cancer cells to TRAIL by promoting the formation of DISC in lipid rafts. Cell Biol Int. 2018 Sep;42(10):1377-1385.
Reference 15 Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma. Neurosci Lett. 2008 Dec 19;448(1):161-5.
Reference 16 Esculetin enhances TRAIL-induced apoptosis through DR5 upregulation in human oral cancer SAS cells. Oral Oncol. 2009 Dec;45(12):1067-72.
Reference 17 Evodiamine sensitizes U87 glioblastoma cells to TRAIL via the death receptor pathway. Mol Med Rep. 2015 Jan;11(1):257-62.
Reference 18 Flavopiridol induces cellular FLICE-inhibitory protein degradation by the proteasome and promotes TRAIL-induced early signaling and apoptosis in breast tumor cells. Cancer Res. 2006 Sep 1;66(17):8858-69.
Reference 19 Sensitization of TRAIL-resistant cervical cancer cells through combination of TRAIL and fucoxanthin treatments. Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5594-5601.
Reference 20 Galangin sensitizes TRAIL-induced apoptosis through down-regulation of anti-apoptotic proteins in renal carcinoma Caki cells. Sci Rep. 2016 Jan 4;6:18642.
Reference 21 Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by promoting the crosstalk of extrinsic and intrinsic apoptotic signalings. Food Chem Toxicol. 2018 Sep;119:334-341.
Reference 22 Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux. Oncol Rep. 2015 Nov;34(5):2692-8.
Reference 23 Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death. Oncol Rep. 2015 May;33(5):2331-6.
Reference 24 Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun. 2008 Oct 10;375(1):129-33.
Reference 25 Combining TRAIL and liquiritin exerts synergistic effects against human gastric cancer cells and xenograft in nude mice through potentiating apoptosis and ROS generation. Biomed Pharmacother. 2017 Sep;93:948-960.
Reference 26 Luteolin enhances TNF-related apoptosis-inducing ligand's anticancer activity in a lung cancer xenograft mouse model. Biochem Biophys Res Commun. 2012 Jan 13;417(2):842-6.
Reference 27 Magnolol Enhances the Therapeutic Effects of TRAIL through DR5 Upregulation and Downregulation of c-FLIP and Mcl-1 Proteins in Cancer Cells. Molecules. 2020 Oct 8;25(19):4591.
Reference 28 Neferine treatment enhances the TRAIL?induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway. Int J Oncol. 2020 May;56(5):1152-1161.
Reference 29 Osthole enhances TRAIL-mediated apoptosis through downregulation of c-FLIP expression in renal carcinoma Caki cells. Oncol Rep. 2017 Apr;37(4):2348-2354.
Reference 30 TRAIL and paclitaxel synergize to kill U87 cells and U87-derived stem-like cells in vitro. Int J Mol Sci. 2012;13(7):9142-56.
Reference 31 Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy. J Exp Clin Cancer Res. 2019 Dec 21;38(1):501.
Reference 32 Phytosphingosine in combination with TRAIL sensitizes cancer cells to TRAIL through synergistic up-regulation of DR4 and DR5. Oncol Rep. 2007 Jan;17(1):175-84.
Reference 33 Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells. Anticancer Res. 2014 Apr;34(4):1893-9.
Reference 34 Pterostilbene Enhances TRAIL-Induced Apoptosis through the Induction of Death Receptors and Downregulation of Cell Survival Proteins in TRAIL-Resistance Triple Negative Breast Cancer Cells. J Agric Food Chem. 2017 Dec 27;65(51):11179-11191.
Reference 35 Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-kappaB signaling. Life Sci. 2018 Sep 1;208:208-220.
Reference 36 Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP. Oncogene. 2005 Jan 27;24(5):838-49.
Reference 37 Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways. BMC Cell Biol. 2018 Dec 29;19(1):29.
Reference 38 Silibinin sensitizes TRAIL-mediated apoptosis by upregulating DR5 through ROS-induced endoplasmic reticulum stress-Ca 2+-CaMKII-Sp1 pathway. Oncotarget. 2017 Dec 7;9(12):10324-10342.
Reference 39 Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis. Clin Cancer Res. 2008 Nov 1;14(21):6855-66.
Reference 40 Triptolide enhances the tumoricidal activity of TRAIL against renal cell carcinoma. FEBS J. 2015 Dec;282(24):4747-4765.
Reference 41 Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells. Mol Carcinog. 2017 Oct;56(10):2190-2199.
Reference 42 Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins. Apoptosis. 2013 May;18(5):618-26.
Reference 43 Morusin Induces TRAIL Sensitization by Regulating EGFR and DR5 in Human Glioblastoma Cells. J Nat Prod. 2016 Feb 26;79(2):317-23.
Reference 44 Shogaol overcomes TRAIL resistance in colon cancer cells via inhibiting of survivin. Tumour Biol. 2015 Nov;36(11):8819-29.
Reference 45 Curcumol Overcomes TRAIL Resistance of Non-Small Cell Lung Cancer by Targeting NRH:Quinone Oxidoreductase 2 (NQO2). Adv Sci (Weinh). 2020 Oct 15;7(22):2002306.
Reference 46 Cyclopamine sensitizes TRAIL-resistant gastric cancer cells to TRAIL-induced apoptosis via endoplasmic reticulum stress-mediated increase of death receptor 5 and survivin degradation. Int J Biochem Cell Biol. 2017 Aug;89:147-156.
Reference 47 Daidzein overcomes TRAIL-resistance in malignant glioma cells by modulating the expression of the intrinsic apoptotic inhibitor, bcl-2. Neurosci Lett. 2009 May 1;454(3):223-8.
Reference 48 Combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in colon cancer HT29 cells. Environ Health Prev Med. 2008 Sep;13(5):281-7.
Reference 49 Aurora kinase inhibitor VE 465 synergistically enhances cytotoxicity of carboplatin in ovarian cancer cells through induction of apoptosis and downregulation of histone 3. Cancer Biol Ther. 2012 Sep;13(11):1034-41.
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