Natural Product (NP) Details

General Information of the NP (ID: NP4621)
Name
Triptolide
Synonyms
Triptolid; PG490; UNII-19ALD1S53J; NSC 163062; CHEMBL463763; CHEBI:9747; 19ALD1S53J; C20H24O6; PG-490; CPD000466307; Triptolide, Tripterygium wilfordii; (-)-Triptolide; PG 490; Trisoxireno(4b,5:6,7:8a,9)phenanthro(1,2-c)furan-1(3H)-one, 3b,4,4a,6,6a,7a,7b,8b,9,10-decahydro-6-hydroxy-8b-methyl-6a-(1-methylethyl)-, (3bS,4aS,5aS,6R,6aR,7aS,7bS,8aS,8bS)-; SMR000466307; NSC163062; Triptolide, 1; Triptolide(PG490)/; AC1Q6AXN; BSPBio_001595; KBioGR_000315; KBioSS_000315
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Species Origin Tripterygium hypoglaucum ...     Click to Show/Hide
Tripterygium hypoglaucum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Celastrales
Family: Celastraceae
Genus: Tripterygium
Species: Tripterygium hypoglaucum
Disease Diabetes mellitus [ICD-11: 5A10] Phase 3 [1]
Structure
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2D MOL

3D MOL

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Formula
C20H24O6
PubChem CID
107985
Canonical SMILES
CC(C)C12C(O1)C3C4(O3)C5(CCC6=C(C5CC7C4(C2O)O7)COC6=O)C
InChI
1S/C20H24O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14,16,22H,4-7H2,1-3H3/t11-,12-,13-,14-,16+,17-,18-,19+,20+/m0/s1
InChIKey
DFBIRQPKNDILPW-CIVMWXNOSA-N
CAS Number
CAS 38748-32-2
Herb ID
HBIN047173
ETMC ID
7086
SymMap ID
SMIT00526
TCMSP ID
MOL003187
TTD Drug ID
D0I6LH
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Temozolomide      Brain cancer     Click to Show/Hide the Molecular Data of This Drug
                 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		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression RELA  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model GIC-1 Glioblastoma multiforme Homo sapiens
                    Experimental
                    Result(s)		 TPL sensitizes GICs to TMZ by synergistically enhancing apoptosis, which is likely resulting from the augmented repression of NF-KappaB signaling.
          BIIB021      Breast cancer     Click to Show/Hide the Molecular Data of This Drug
                 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 AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EIF4EBP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p105  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model 8505C CVCL_1054 Thyroid gland anaplastic carcinoma Homo sapiens
TPC-1 CVCL_6298 Thyroid gland papillary carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-KappaB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells.
          Venetoclax      Chronic lymphocytic leukaemia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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
                    Molecule(s)
                    Regulation		 Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Up-regulation Expression BID  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression PMAIP1  Molecule Info 
Pathway MAP
                    In-vitro Model MV4-11 CVCL_0064 Childhood acute monocytic leukemia Homo sapiens
MOLM-13 CVCL_2119 Adult acute myeloid leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
THP-1 CVCL_0006 Childhood acute monocytic leukemia Homo sapiens
KG-1a CVCL_1824 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of Bcl-2 family proteins and activation of the intrinsic apoptotic pathway.
          Cetuximab      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression POLR2A  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
UM-SCC-6 CVCL_7773 Tongue squamous cell carcinoma Homo sapiens
NCI-H520 CVCL_1566 Lung squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Cetuximab-Triptolide conjugate suppresses the growth of EGFR-overexpressing lung cancers through targeting RNA polymerase II.
          Oxaliplatin      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Down-regulation Expression LEF1  Molecule Info 
Pathway MAP
Down-regulation Expression TCF7  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
                    In-vivo Model SW480 cells were subcutaneously injected into the back of the mice (2*106 cells in 200 mL of medium).
                    Experimental
                    Result(s)		 Triptolide synergistically enhances antitumor activity of oxaliplatin in colon carcinoma in vitro and in vivo.
          Tumor necrosis factor alpha      Colorectal cancer     Click to Show/Hide the Molecular Data of This Drug
                 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		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage COL11A2  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Triptolide sensitized human breast cancer cells to TNF Alpha induced apoptosis.
          Erlotinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combined treatment with triptolide and tyrosine kinase inhibitors synergistically enhances apoptosis in non-small cell lung cancer H1975 cells but not H1299 cells through EGFR/Akt pathway.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 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.
          AMD3100      Malignant haematopoietic neoplasm     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CBY1  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression STAT3  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model MG-63 CVCL_0426 Osteosarcoma Homo sapiens
U2OS CVCL_0042 Osteosarcoma Homo sapiens
SaOS-2 CVCL_0548 Osteosarcoma Homo sapiens
143B CVCL_2270 Osteosarcoma Homo sapiens
HOS-8603 Osteosarcoma Homo sapiens
                    Experimental
                    Result(s)		 AMD3100 combined with triptolide can reduce proliferation and metastasis, and induce apoptosis of U2OS cells, which may be related to the Erk1/2, Akt, STAT3 and NF-KappaB pathways.
          Aspirin      Pain     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression CCNE1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  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
                    Experimental
                    Result(s)		 Aspirin and triptolide combination treatment has synergistic anti-tumor effects on cervical cancer cells.
          Vasostatin      Pancreatic endocrine tumor     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 BAD  Molecule Info 
Pathway MAP
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 BIRC2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  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 A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HEK293 CVCL_0045 Healthy Homo sapiens
QSG-7701 CVCL_6944 Human hepatocarcinoma Homo sapiens
HUVEC CVCL_2959 Healthy Homo sapiens
                    In-vivo Model HCT116 cells in a solution containing 25 ml of culture medium and 25 ml of mouse sarcoma extracellular matrix (Matrigel) were injected subcutaneously into the dorsal flanks of mice.
                    Experimental
                    Result(s)		 Herbal compound triptolide synergistically enhanced antitumor activity of vasostatin120-180.
          5-LOX shRNA      Prostate cancer     Click to Show/Hide the Molecular Data of This Drug
                 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		 Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vivo Model 1*107 SW1990 cells in 100 uL phosphate-buffered saline (PBS) were injected into back of BALB/c nude mice.
                    Experimental
                    Result(s)		 Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model.
          Lcotinib      Pulmonary hypertension     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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 Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combined treatment with triptolide and tyrosine kinase inhibitors synergistically enhances apoptosis in non-small cell lung cancer H1975 cells but not H1299 cells through EGFR/Akt pathway.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 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		 Down-regulation Activity p105  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 Athymic nude mice were injected with 5*106 HuH-7 cells subcutaneously in the right flank in 100-mL aliquots mixed with Matrigel in 1:1 ratio.
                    Experimental
                    Result(s)		 The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis and decreasing viability, whereas triptolide alone was sufficient to decrease nuclear factor kappaB activity.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation ROS generation
                    In-vitro Model NCI-H630 CVCL_1572 Colorectal cancer Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
RKO CVCL_0504 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)		 PG490 strongly enhanced the cytotoxicity of 5-FU. PG490 also simultaneously induced ROS and inhibited NF-KappaB activity and significantly enhanced the cytotoxic effect of 5-FU in three CRC cell lines in vitro.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     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		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CHK1  Molecule Info 
Pathway MAP
Up-regulation Expression H2AFX  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Triptolide synergistically increased gemcitabine-induced cell growth inhibition and apoptosis, in addition to the cooperative regulation of B-cell lymphoma 2 family proteins and loss of mitochondrial membrane potential.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     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		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Up-regulation Expression GSK-3B  Molecule Info 
Pathway MAP
Up-regulation Expression JNK1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JUN  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model RT-112 CVCL_1670 Bladder carcinoma Homo sapiens
RT-4 CVCL_0036 Bladder carcinoma Homo sapiens
KK47 CVCL_8253 Bladder carcinoma Homo sapiens
TCCSUP CVCL_1738 Bladder carcinoma Homo sapiens
EJ CVCL_ZC18 B-cell lymphoma Homo sapiens
J82 CVCL_0359 Bladder carcinoma Homo sapiens
                    In-vivo Model To produce a subcutaneous xenograft model, RT112 cells (5*106) were injected into the subcutaneous tissue of pathogen-free 6-week-old BALB/cAJcl-nu/nu mice.
                    Experimental
                    Result(s)		 Cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer through an interaction of inactivated glycogen synthase kinase-3beta with p53.
          Gefitinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     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		 Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI1  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model The A549/siE-cad cells (2*106) were injected subcutaneously into the underarms of the right forelimbs of 6-week-old BCLB/c mice.
                    Experimental
                    Result(s)		 Triptolide inhibits epithelial mesenchymal transition and induces apoptosis in gefitinib resistant lung cancer cells.
          Cytarabine      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     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		 Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CHK1  Molecule Info 
Pathway MAP
Up-regulation Expression H2AFX  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RAD53  Molecule Info 
Pathway MAP
                    In-vitro Model NALM-6 CVCL_0092 Adult B acute lymphoblastic leukemia Homo sapiens
                    In-vivo Model To generate a mouse model of araC-resistant ALL, NALM-6/R cells (5 * 105) were subcutaneously injected into the angular veins of sublethally irradiated adult NSI (NOD/SCID IL2rg-/-) mice (20-30 g body weight, 2-3 months of age).
                    Experimental
                    Result(s)		 Low dose triptolide reverses chemoresistance in adult acute lymphoblastic leukemia cells via reactive oxygen species generation and DNA damage response disruption.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     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		 Up-regulation Expression CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation CHK1  Molecule Info 
Pathway MAP
Up-regulation Expression H2AFX  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RAD53  Molecule Info 
Pathway MAP
                    In-vitro Model NALM-6 CVCL_0092 Adult B acute lymphoblastic leukemia Homo sapiens
                    In-vivo Model To generate a mouse model of araC-resistant ALL, NALM-6/R cells (5 * 105) were subcutaneously injected into the angular veins of sublethally irradiated adult NSI (NOD/SCID IL2rg-/-) mice (20-30 g body weight, 2-3 months of age).
                    Experimental
                    Result(s)		 Low dose triptolide reverses chemoresistance in adult acute lymphoblastic leukemia cells via reactive oxygen species generation and DNA damage response disruption.
Target and Pathway
Target(s) Nuclear factor NF-kappa-B (NFKB)  Molecule Info  [20]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 NF-kappa B signaling pathway
3 Osteoclast differentiation
4 Legionellosis
5 HTLV-I infection
6 Epstein-Barr virus infection
7 Pathways in cancer
8 Viral carcinogenesis
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 B cell activation
3 Inflammation mediated by chemokine and cytokine signaling pathway
4 T cell activation
5 Toll receptor signaling pathway
Pathwhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine Click to Show/Hide
2 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Pathway Interaction Database IL12-mediated signaling events Click to Show/Hide
2 Alternative NF-kappaB pathway
Reactome RIP-mediated NFkB activation via ZBP1 Click to Show/Hide
2 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
3 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
4 Interleukin-1 processing
5 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
6 IkBA variant leads to EDA-ID
7 Dectin-1 mediated noncanonical NF-kB signaling
8 NIK-->noncanonical NF-kB signaling
9 TRAF6 mediated NF-kB activation
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 DNA Damage Response (only ATM dependent)
3 SIDS Susceptibility Pathways
4 Nuclear Receptors Meta-Pathway
5 Cytosolic sensors of pathogen-associated DNA
6 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
7 EBV LMP1 signaling
8 TNF alpha Signaling Pathway
9 TSLP Signaling Pathway
10 Neural Crest Differentiation
11 TWEAK Signaling Pathway
12 RANKL/RANK Signaling Pathway
13 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
14 Interleukin-1 processing
15 Folate Metabolism
16 Vitamin B12 Metabolism
17 Selenium Micronutrient Network
18 Regulation of toll-like receptor signaling pathway
References
Reference 1 ClinicalTrials.gov (NCT02115659) Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD). U.S. National Institutes of Health.
Reference 2 Triptolide synergistically enhances temozolomide-induced apoptosis and potentiates inhibition of NF-KappaB signaling in glioma initiating cells. Am J Chin Med. 2014;42(2):485-503.
Reference 3 Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-KappaB signal pathways in thyroid carcinoma cells. Biomed Pharmacother. 2016 Oct;83:22-32.
Reference 4 Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of Bcl-2 family proteins and activation of the intrinsic apoptotic pathway. Cell Death Dis. 2020 Jul 22;11(7):555.
Reference 5 Cetuximab-Triptolide Conjugate Suppresses the Growth of EGFR-Overexpressing Lung Cancers through Targeting RNA Polymerase II. Mol Ther Oncolytics. 2020 Jul 6;18:304-316.
Reference 6 Triptolide synergistically enhances antitumor activity of oxaliplatin in colon carcinoma in vitro and in vivo. DNA Cell Biol. 2014 Jul;33(7):418-25.
Reference 7 Triptolide sensitizes human breast cancer cells to tumor necrosis factor?Alpha?induced apoptosis by inhibiting activation of the nuclear factor?KappaB pathway. Mol Med Rep. 2016 Apr;13(4):3257-64.
Reference 8 Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway. Chem Pharm Bull (Tokyo). 2019 Aug 1;67(8):864-871.
Reference 9 Triptolide enhances the tumoricidal activity of TRAIL against renal cell carcinoma. FEBS J. 2015 Dec;282(24):4747-4765.
Reference 10 AMD3100 combined with triptolide inhibit proliferation, invasion and metastasis and induce apoptosis of human U2OS osteosarcoma cells. Biomed Pharmacother. 2017 Feb;86:677-685.
Reference 11 Enhanced anti-tumor efficacy of aspirin combined with triptolide in cervical cancer cells. Asian Pac J Cancer Prev. 2013;14(5):3041-4.
Reference 12 Herbal compound triptolide synergistically enhanced antitumor activity of vasostatin120-180. Anticancer Drugs. 2013 Oct;24(9):945-57.
Reference 13 Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model. Cancer Chemother Pharmacol. 2012 Jan;69(1):253-61.
Reference 14 Sorafenib and triptolide as combination therapy for hepatocellular carcinoma. Surgery. 2014 Aug;156(2):270-9.
Reference 15 Triptolide simultaneously induces reactive oxygen species, inhibits NF-kappaB activity and sensitizes 5-fluorouracil in colorectal cancer cell lines. Cancer Lett. 2010 May 28;291(2):200-8.
Reference 16 Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett. 2016 May;11(5):3527-3533.
Reference 17 Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3beta with p53. Oncogene. 2008 Jul 31;27(33):4603-14.
Reference 18 Triptolide inhibits epithelial?mesenchymal transition and induces apoptosis in gefitinib?resistant lung cancer cells. Oncol Rep. 2020 May;43(5):1569-1579.
Reference 19 Low dose triptolide reverses chemoresistance in adult acute lymphoblastic leukemia cells via reactive oxygen species generation and DNA damage response disruption. Oncotarget. 2016 Dec 20;7(51):85515-85528.
Reference 20 Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells. Oncogene. 2001 Nov 29;20(55):8009-18.
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