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Natural Product (NP) Details

General Information of the NP (ID: NP2960)
Name
Epigallocatechin gallate
Synonyms
(-)-Epigallocatechin gallate; EGCG; 989-51-5; Epigallocatechin 3-gallate; Epigallocatechin-3-gallate; Tea catechin; (-)-Epigallocatechin-3-o-gallate; Teavigo; Epigallocatechin-3-monogallate; (-)-Epigallocatechol gallate; (2R,3R)-5,7-Dihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-3-yl 3,4,5-trihydroxybenzoate; Catechin deriv; UNII-BQM438CTEL; Green tea extract; CCRIS 3729; (-)-epigallocatechin 3-gallate; C22H18O11; BQM438CTEL; (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl; EGCG analogs; EGCG, Anagen; Epigallocatechin gallate analogs, Anagen; Epigallocatechin gallate, Anagen; GTPs,Anagen; Green tea polyphenols, Anagen; EPIGALOCATECHIN GALLATE
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Species Origin Hamamelis virginiana ...     Click to Show/Hide
Hamamelis virginiana
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Saxifragales
Family: Hamamelidaceae
Genus: Hamamelis
Species: Hamamelis virginiana
Disease Hepatic fibrosis/cirrhosis [ICD-11: DB93] Phase 3 [1]
Discovery agent [ICD-11: N.A.] Investigative [2]
Structure
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2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C22H18O11
PubChem CID
65064
Canonical SMILES
C1C(C(OC2=CC(=CC(=C21)O)O)C3=CC(=C(C(=C3)O)O)O)OC(=O)C4=CC(=C(C(=C4)O)O)O
InChI
1S/C22H18O11/c23-10-5-12(24)11-7-18(33-22(31)9-3-15(27)20(30)16(28)4-9)21(32-17(11)6-10)8-1-13(25)19(29)14(26)2-8/h1-6,18,21,23-30H,7H2/t18-,21-/m1/s1
InChIKey
WMBWREPUVVBILR-WIYYLYMNSA-N
CAS Number
CAS 989-51-5
Herb ID
HBIN025354
TTD Drug ID
D0U2BH
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Interferon alpha-2b      Acute lymphoblastic leukemia     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model A-375 CVCL_0132 Amelanotic melanoma Homo sapiens
G-361 CVCL_1220 Melanoma Homo sapiens
Hs 294T CVCL_0331 Melanoma Homo sapiens
                    In-vivo Model Female nu/nu athymic nude mice (6-weeks old) were subcutaneously implanted with 0.5*106 Hs-294T melanoma cells with equal volume of matrigel (in 100L) on the left flanks.
                    Experimental
                    Result(s)
EGCG sensitizes melanoma cells to interferon induced growth inhibition in a mouse model of human melanoma.
          Sodium butyrate      Acute myeloid leukemia     Click to Show/Hide the Molecular Data of This Drug
                 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
                    Molecule(s)
                    Regulation
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression DNMT1  Molecule Info 
Pathway MAP
Down-regulation Expression HDAC1  Molecule Info 
Pathway MAP
Up-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Induction Cell cycle arrest in G2/M phase
                    In-vitro Model RKO CVCL_0504 Colon carcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
At low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells.
          Temozolomide      Brain cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Expression HSPA5  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
LN-229 CVCL_0393 Glioblastoma Homo sapiens
                    In-vivo Model 2*105 cells (U87 and U251) in a volume of 10L were injected into the right frontal lobe of the brain and thereafter the skin incision was sutured with silk thread in athymic mice.
                    Experimental
                    Result(s)
Green tea epigallocatechin gallate enhances therapeutic efficacy of temozolomide in orthotopic mouse glioblastoma models.
          6-OH-11-O-Hydroxyphenanthrene      Breast cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
Down-regulation Expression COX-2  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 MYCN  Molecule Info 
Pathway MAP
                    In-vitro Model SK-N-BE(2)-C CVCL_0529 Neuroblastoma Homo sapiens
                    Experimental
                    Result(s)
Epigallocatechin-3-gallate and 6-OH-11-O-hydroxyphenanthrene limit BE(2)-C neuroblastoma cell growth and neurosphere formation in vitro.
          Tamoxifen      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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression CYP1B1  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  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
                    In-vivo Model Female CD1 athymic nude mice were inoculated into the right flank with MDA-MB-231 cells (2*106/50L matrigel), which were left to form palpable tumours.
                    Experimental
                    Result(s)
Tamoxifen at realistic doses (75 mug kg(-1)) can suppress the growth of ER-negative breast cancer when combined with EGCG. The dominant mechanism for tumour suppression is the concomitant decrease in tumour protein expressions of mTOR and the EGFR.
          N-(4-hydroxyphenyl) retinamide      Cervical cancer     Click to Show/Hide the Molecular Data of This Drug
                 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 microRNA 106b  Molecule Info 
Pathway MAP
Up-regulation Expression microRNA 34a  Molecule Info 
Pathway MAP
Up-regulation Expression microRNA 7-1  Molecule Info 
Pathway MAP
Down-regulation Expression microRNA 92b  Molecule Info 
Pathway MAP
Down-regulation Expression microRNA 93  Molecule Info 
Pathway MAP
Up-regulation Expression microRNA 99a  Molecule Info 
Pathway MAP
                    In-vitro Model SK-N-BE(2) CVCL_0528 Neuroblastoma Homo sapiens
IMR-32 CVCL_0346 Neuroblastoma Homo sapiens
                    Experimental
                    Result(s)
Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells.
          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 [9]
                    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 CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model Tu 177 CVCL_4913 Laryngeal squamous cell carcinoma Homo sapiens
Tu 212 CVCL_4915 Head and neck squamous cell carcinoma Homo sapiens
MDA-886Ln CVCL_6987 Laryngeal squamous cell carcinoma Homo sapiens
SqCC/Y1 CVCL_0551 Oral cavity squamous cell carcinoma Homo sapiens
                    In-vivo Model Animal models were constructed by injecting Tu212 cells (2*106) into the right flank of nude mice (athymic nu/nu).
                    Experimental
                    Result(s)
The combined treatment resulted in significantly greater inhibition of tumor growth and delayed tumor progression as a result of increased apoptosis, decreased cell proliferation and reduced pEGFR and pAKT compared to the single agent treatment groups.
          Leptomycin B      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 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
Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression CYP3A43  Molecule Info 
Pathway MAP
Down-regulation Expression GPX1  Molecule Info 
Pathway MAP
Down-regulation Expression SOD Cu-Zn  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Up-regulation ROS generation
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Combination treatment of LMB and EGCG augments LMB-induced cytotoxicity through enhanced ROS production and the modulation of drug metabolism and p21/survivin pathways.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 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 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.
          Bortezomib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 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 Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression and phosphorylation RELA  Molecule Info 
Pathway MAP
                    In-vitro Model KM-3 CVCL_0011 Multiple myeloma Homo sapiens
                    Experimental
                    Result(s)
Combined EGCG and bortezomib showed synergistic anticancer effect partly via regulating NF-kappaB pathway.
          Ponatinib      Mantle cell lymphoma     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 CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression MPIP1  Molecule Info 
Pathway MAP
Up-regulation Expression TGFB2  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)
Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes.
          Dacarbazine      Melanoma     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Phosphorylation FAK  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation MMP-9  Molecule Info 
Pathway MAP
                    In-vitro Model B16 CVCL_F936 Mouse melanoma Mus musculus
                    In-vivo Model Animal models were constructed by injecting intraperitoneally B16-F3m cells (2*106) into Balb/c mice.
                    Experimental
                    Result(s)
Combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.
          Vorinostat      Mycosis fungoides     Click to Show/Hide the Molecular Data of This Drug
                 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
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP7  Molecule Info 
Pathway MAP
Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCNA1  Molecule Info 
Pathway MAP
Down-regulation Expression CDK2  Molecule Info 
Pathway MAP
Down-regulation Expression CDK4  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
                    In-vitro Model A-375 CVCL_0132 Amelanotic melanoma Homo sapiens
Hs 294T CVCL_0331 Melanoma Homo sapiens
G-361 CVCL_1220 Melanoma Homo sapiens
                    Experimental
                    Result(s)
The combination treatment resulted in significantly greater inhibition of cell proliferation, increased apoptosis, activation of p21, p27 and caspases (3, 7 and 9) and Bax as well as down-regulation of cdk2, cdk4, cyclin A, NF-kappaB protein p65/RelA and Bcl2 protein and transcript.
          Raloxifene      Osteoporosis     Click to Show/Hide the Molecular Data of This Drug
                 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
Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation JNK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
The combination of EGCG and raloxifene effectively reduced the mitogenic and survival signaling in MDA-MB-231 cells.
          Ibuprofen      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 [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Expression TP53  Molecule Info 
Pathway MAP
                    In-vitro Model DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)
EGCG+ibuprofen treatment has a synergistic effect on apoptosis, and xidative stress, directly or indirectly via ceramide synthesis mediated pro-apoptotic signaling.
          ONO-8711      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 [18]
                    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 CASP3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Induction Cell cycle arrest in G2/M phase
Up-regulation Ratio of Bax to Bcl-2
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)
ONO-8711 significantly inhibited PGE2-induced HCC proliferation while increased the inhibitory effect of EGCG on HCC cell viability and migration ability compared with EGCG alone.
          Bicalutamide      Prostate cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Expression SOD Mn  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Up-regulation Apoptosis
                    In-vitro Model NRP-152 CVCL_4869 Healthy Rattus norvegicus
NRP-154 CVCL_4870 Healthy Rattus norvegicus
                    Experimental
                    Result(s)
Epigallocatechin-3-gallate and bicalutamide cause growth arrest and apoptosis in NRP-152 and NRP-154 prostate epithelial cells.
          Celecoxib      Rheumatoid arthritis     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 [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression IL6  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-2  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model COLO 357 CVCL_0221 Pancreatic adenosquamous carcinoma Homo sapiens
                    Experimental
                    Result(s)
EGCG synergistically boosts celecoxib-mediated effects and reduces the levels of celecoxib required to elicit beneficial effects on tumorigenic mediators by a factor of ten.
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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 Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
MIA PaCa-2 CVCL_0428 Pancreatic ductal adenocarcinoma Homo sapiens
BxPC-3 CVCL_0186 Pancreatic ductal adenocarcinoma Homo sapiens
HPAF-II CVCL_0313 Pancreatic ductal adenocarcinoma Homo sapiens
CFPAC-1 CVCL_1119 Cystic fibrosis Homo sapiens
SU.86.86 CVCL_3881 Pancreatic adenocarcinoma Homo sapiens
KPC3 CVCL_A9ZK Mouse pancreatic neoplasm Mus musculus
                    In-vivo Model C57BL/6J mice (4-6 weeks) were injected subcutaneously with 0.3*106 KPC cells per tumor suspended in 100L of sterile PBS.
                    Experimental
                    Result(s)
EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial-mesenchymal transition markers and inhibiting Akt pathway.
          Trichostatin A      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 [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression CDKN2A  Molecule Info 
Pathway MAP
                    In-vitro Model CA46 CVCL_1101 Burkitt lymphoma Homo sapiens
                    Experimental
                    Result(s)
Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a.
          SU5416      Thrombocytopenia     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 [23]
                    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 Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression CDK2  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
Down-regulation Expression FGF2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model SH-SY5Y CVCL_0019 Neuroblastoma Homo sapiens
SK-N-BE(2) CVCL_0528 Neuroblastoma Homo sapiens
                    Experimental
                    Result(s)
SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells.
          Enoxacin      Urinary tract infection     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 [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
C-33 A CVCL_1094 Cervical squamous cell carcinoma Homo sapiens
WI-38 CVCL_0579 Healthy Homo sapiens
                    Experimental
                    Result(s)
EGCG functions synergistically against cancer cell proliferation in combined treatment with enoxacin.
          4-hydroxy-tamoxifen      Cyclic Mastalgia     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 [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation
Induction Apoptosis
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
The synergistic cytotoxicity elicited by the combination of EGCG and 4-OHT results from an earlier induction of apoptosis but this was not caused by an increase in G1-arrest or 4-OHT-mediated changes in the metabolism of EGCG.
          Sulindac      Rheumatoid arthritis     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 [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation
Up-regulation Apoptosis
                    In-vivo Model Colon carcinogenesis in five-week-old male was induced by azoxymethane.
                    Experimental
                    Result(s)
EGCG with sulindac synergistically suppresses ACF formation by enhancing apoptosis.
          Tapentadol      Acute pain     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     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
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
EGCG and TAP reduced the proliferation of MDA-MB-231 cells by impairing cell-cycle progression.
    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 [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression AXL  Molecule Info 
Pathway MAP
Down-regulation Expression TYRO3  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
                    Experimental
                    Result(s)
Reversal of cisplatin resistance by epigallocatechin gallate is mediated by downregulation of axl and tyro 3 expression in human lung cancer cells.
          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 [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model A549 cells were injected subcutaneously (1*106, 100 uL of PBS) into the left flanks of the 7-8-week old BALB/C male nude mice.
                    Experimental
                    Result(s)
EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC.
          5-fluorouracil      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 [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
Down-regulation Expression TFAP2A  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
                    In-vivo Model Exponentially growing SCG7901/FU cells (5*106) were injected subcutaneously into the dorsum of female BALB/c nude mice.
                    Experimental
                    Result(s)
Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer.
          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 [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation
Up-regulation DOX accumulation
                    In-vitro Model KB-A1 CVCL_1D82 Human oral epidermoid carcinoma Homo sapiens
                    In-vivo Model About 5 x106 cells were subcutaneously injected into the right flank of the athymic male nude mice.
                    Experimental
                    Result(s)
EGCG could chemosensitize resistant tumor cells to DOX in vivo through an increase in the accumulation of DOX in the tumors.
Target and Pathway
Target(s) Fatty acid synthase (FASN)  Molecule Info  [32]
HIV reverse transcriptase (HIV RT)  Molecule Info  [33]
Matrix metalloproteinase-14 (MMP-14)  Molecule Info  [34]
Matrix metalloproteinase-2 (MMP-2)  Molecule Info  [34]
Neutrophil elastase (NE)  Molecule Info  [35]
Plasmodium 3-oxoacyl-acyl-carrier reductase (Malaria fabG)  Molecule Info  [32]
Plasmodium enoyl-ACP reductase (Malaria fabI)  Molecule Info  [36]
Plasmodium Fatty acid synthesis protein (Malaria FabZ)  Molecule Info  [32]
Squalene monooxygenase (SQLE)  Molecule Info  [2]
BioCyc Fatty acid biosynthesis initiation Click to Show/Hide
2 Fatty acid elongation -- saturated
3 Palmitate biosynthesis
KEGG Pathway Fatty acid biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Fatty acid metabolism
4 AMPK signaling pathway
5 Insulin signaling pathway
6 Leukocyte transendothelial migration
7 GnRH signaling pathway
8 Estrogen signaling pathway
9 Pathways in cancer
10 Proteoglycans in cancer
11 Bladder cancer
12 Transcriptional misregulation in cancer
13 Systemic lupus erythematosus
14 Steroid biosynthesis
15 Sesquiterpenoid and triterpenoid biosynthesis
16 Metabolic pathways
17 Biosynthesis of secondary metabolites
18 Biosynthesis of antibiotics
19 TNF signaling pathway
20 Fatty acid biosynthesis
21 Biotin metabolism
22 Metabolic pathways
23 Fatty acid metabolism
NetPath Pathway Leptin Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 ID Signaling Pathway
Panther Pathway Alzheimer disease-presenilin pathway Click to Show/Hide
Pathwhiz Pathway Fatty Acid Biosynthesis Click to Show/Hide
2 Steroid Biosynthesis
Pathway Interaction Database p73 transcription factor network Click to Show/Hide
2 Validated transcriptional targets of deltaNp63 isoforms
3 LPA receptor mediated events
4 Plasma membrane estrogen receptor signaling
5 Osteopontin-mediated events
6 Validated transcriptional targets of AP1 family members Fra1 and Fra2
7 Angiopoietin receptor Tie2-mediated signaling
8 Direct p53 effectors
9 amb2 Integrin signaling
10 ATF-2 transcription factor network
11 FOXM1 transcription factor network
12 Regulation of nuclear beta catenin signaling and target gene transcription
13 Syndecan-2-mediated signaling events
14 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
15 C-MYB transcription factor network
16 HIF-2-alpha transcription factor network
17 Signaling events mediated by focal adhesion kinase
Reactome ChREBP activates metabolic gene expression Click to Show/Hide
2 Activation of gene expression by SREBF (SREBP)
3 Fatty Acyl-CoA Biosynthesis
4 Collagen degradation
5 Degradation of the extracellular matrix
6 Activation of Matrix Metalloproteinases
7 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
8 EPH-ephrin mediated repulsion of cells
9 Cholesterol biosynthesis
WikiPathways Fatty Acid Biosynthesis Click to Show/Hide
2 Nuclear Receptors Meta-Pathway
3 Liver X Receptor Pathway
4 Activation of Gene Expression by SREBP (SREBF)
5 SREBF and miR33 in cholesterol and lipid homeostasis
6 SREBP signalling
7 Metabolism of water-soluble vitamins and cofactors
8 Integration of energy metabolism
9 Fatty acid, triacylglycerol, and ketone body metabolism
10 AMPK Signaling
11 Activation of Matrix Metalloproteinases
12 AGE/RAGE pathway
13 Matrix Metalloproteinases
14 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
15 Human Complement System
16 Degradation of collagen
17 Senescence and Autophagy in Cancer
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7002).
Reference 2 Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate squalene epoxidase. J Nat Prod. 2001 Aug;64(8):1010-4.
Reference 3 (-)-Epigallocatechin-3-gallate (EGCG) sensitizes melanoma cells to interferon induced growth inhibition in a mouse model of human melanoma. Cell Cycle. 2009 Jul 1;8(13):2057-63.
Reference 4 Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. Exp Cell Res. 2014 May 15;324(1):40-53.
Reference 5 Green tea epigallocatechin gallate enhances therapeutic efficacy of temozolomide in orthotopic mouse glioblastoma models. Cancer Lett. 2011 Mar 28;302(2):100-8.
Reference 6 Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro. Nutrients. 2018 Aug 22;10(9):1141.
Reference 7 A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate. Br J Cancer. 2008 Oct 7;99(7):1056-63.
Reference 8 Alterations in expression of specific microRNAs by combination of 4-HPR and EGCG inhibited growth of human malignant neuroblastoma cells. Brain Res. 2012 May 15;1454:1-13.
Reference 9 Synergistic inhibition of head and neck tumor growth by green tea (-)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor. Int J Cancer. 2008 Sep 1;123(5):1005-14.
Reference 10 Epigallocatechin-3-gallate enhances the therapeutic effects of leptomycin B on human lung cancer a549 cells. Oxid Med Cell Longev. 2015;2015:217304.
Reference 11 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 12 Potentiation of (-)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells. Acta Biochim Biophys Sin (Shanghai). 2009 Dec;41(12):1018-26.
Reference 13 Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes. J BUON. Oct-Dec 2014;19(4):992-8.
Reference 14 Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice. J Cell Biochem. 2001;83(4):631-42.
Reference 15 Anti-melanoma effects of vorinostat in combination with polyphenolic antioxidant (-)-epigallocatechin-3-gallate (EGCG). Pharm Res. 2010 Jun;27(6):1103-14.
Reference 16 In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells. Oncol Rep. 2010 Sep;24(3):779-85.
Reference 17 Synergistic cell death by EGCG and ibuprofen in DU-145 prostate cancer cell line. Anticancer Res. Nov-Dec 2007;27(6B):3947-56.
Reference 18 Synergetic Effect of EP1 Receptor Antagonist and (-)-Epigallocatechin-3-gallate in Hepatocellular Carcinoma. Pharmacology. 2019;104(5-6):267-275.
Reference 19 Epigallocatechin-3-gallate and bicalutamide cause growth arrest and apoptosis in NRP-152 and NRP-154 prostate epithelial cells. Int J Urol. 2007 Jun;14(6):545-51.
Reference 20 (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. Eur J Pharmacol. 2012 Jun 5;684(1-3):36-43.
Reference 21 Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial-Mesenchymal Transition: Enhanced Efficacy when Combined with Gemcitabine. Nutrients. 2019 Aug 9;11(8):1856.
Reference 22 Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a. Oncol Rep. 2013 Dec;30(6):2969-75.
Reference 23 SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Neurochem Res. 2011 Aug;36(8):1383-96.
Reference 24 Enoxacin and Epigallocatechin Gallate (EGCG) Act Synergistically to Inhibit the Growth of Cervical Cancer Cells in Culture. Molecules. 2019 Apr 22;24(8):1580.
Reference 25 Potential mechanisms for the synergistic cytotoxicity elicited by 4-hydroxytamoxifen and epigallocatechin gallate in MDA-MB-231 cells. Int J Oncol. 2007 Jun;30(6):1407-12.
Reference 26 Synergistic effects of (-)-epigallocatechin gallate with sulindac against colon carcinogenesis of rats treated with azoxymethane. Cancer Lett. 2002 Mar 8;177(1):49-56.
Reference 27 Shining a Light on the Effects of the Combination of (-)-Epigallocatechin-3-gallate and Tapentadol on the Growth of Human Triple-negative Breast Cancer Cells. In Vivo. Sep-Oct 2019;33(5):1463-1468.
Reference 28 Reversal of Cisplatin resistance by epigallocatechin gallate is mediated by downregulation of axl and tyro 3 expression in human lung cancer cells. Korean J Physiol Pharmacol. 2014 Feb;18(1):61-6.
Reference 29 EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC. Onco Targets Ther. 2019 Jul 26;12:6033-6043.
Reference 30 Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer. Oncotarget. 2017 Sep 6;8(47):82842-82853.
Reference 31 In vivo reversal of doxorubicin resistance by (-)-epigallocatechin gallate in a solid human carcinoma xenograft. Cancer Lett. 2004 May 28;208(2):179-86.
Reference 32 Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53.
Reference 33 Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase. Bioorg Med Chem Lett. 2001 Oct 22;11(20):2763-7.
Reference 34 Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4.
Reference 35 Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
Reference 36 Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR). J Med Chem. 2007 Feb 22;50(4):765-75.
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Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China