Pair Name	Epigallocatechin gallate, Metformin
Partner Name	Metformin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G0/G1 phase
Gene Regulation	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	GPC3	hsa2719
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study

Pair Name	Epigallocatechin gallate, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
	Down-regulation	Expression	ABCB1	hsa5243
	Up-regulation	Expression	BAD	hsa572
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	HSPA5	hsa3309
	Up-regulation	Expression	MIR155	hsa406947
	Up-regulation	Activity	NFKB1	hsa4790
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens (Human)	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	Our data show that EGCG may be act as a novel chemo-sensitizer, and the GRP78/NF-κB/miR-155-5p/MDR1 pathway plays a vital role in EGCG enhancing the sensitivity of colorectal cancer to 5-FU.

Pair Name	Epigallocatechin gallate, Vorinostat
Partner Name	Vorinostat
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BIRC3	hsa330
	Up-regulation	Expression	CASP7	hsa840
In Vitro Model	MDA-MB-157	Breast carcinoma	Homo sapiens (Human)	CVCL_0618
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	HCC1806	Breast squamous cell carcinoma, acantholytic variant	Homo sapiens (Human)	CVCL_1258
Result	The compounds were able to decrease the expression of cIAP2 while increasing the expression of pro-apoptotic caspase 7. There were also changes in histone modifications, suggesting a role of epigenetic mechanisms in these changes in expression of cIAP2. These changes resulted in an increase in apoptosis. SAHA and EGCG were also capable of limiting TNBC cell migration across a fibronectin (FN) matrix.

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Activity	DLL3	hsa10683
	Down-regulation	Activity	NOTCH3	hsa4854
	Down-regulation	Expression	SOX2-OT	KEGG ID N.A.
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens (Human)	CVCL_0548
In Vivo Model	1×10⁵ indicated cells were inoculated subcutaneously into the inguinal folds of NOD/SCID mice.
Result	SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Pair Name	Epigallocatechin gallate, Irinotecan
Partner Name	Irinotecan
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induced-->GRP78-mediated endoplasmic reticulum stress
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Expression	GRP78	KEGG ID N.A.
	Down-regulation	Expression	ROS1	hsa6098
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
	RKO	Colon carcinoma	Homo sapiens (Human)	CVCL_0504
In Vivo Model	The concentration of HCT116 cells in the logarithmic phase was adjusted to 2.5×10⁷/mL, and the 200 μL cell suspension was inoculated subcutaneously on the right dorsal side of the mouse. When the average tumor volume reached 100 mm3, animals were randomized into 4 groups (5 mice for each group), control (Control, normal saline, 1 time per day, ip), irinotecan (IRI, 4 mg/kg irinotecan, 2 times per week, ip), EGCG (EGCG, 5 mg/kg, 1 time per day, ip), and irinotecan in combination with EGCG (IRI + EGCG).
Result	These reults confirmed that EGCG alone or in combination with irinotecan could up-regulate the GRP78, activate ERS of colorectal cancer cells, reduce intracellular reactive oxygen species and mitochondrial membrane potential, and induce apoptosis. The mouse xenograft experiment also confirmed the synergistic effect of EGCG and irinotecan on ERS and tumor cell.EGCG can induce GRP78-mediated endoplasmic reticulum stress and enhance the chemo-sensitivity of colorectal cancer cells when coadministered with irinotecan.

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	ANGPT1	hsa284
	Down-regulation	Expression	BAD	hsa572
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BIRC3	hsa330
	Down-regulation	Expression	BIRC5	hsa332
	Down-regulation	Expression	CASP3	hsa836
	Down-regulation	Expression	CASP6	hsa839
	Down-regulation	Expression	CASP8	hsa841
	Down-regulation	Expression	CASP9	hsa842
	Down-regulation	Expression	MMP2	hsa4313
	Down-regulation	Expression	MMP3	hsa4314
	Down-regulation	Expression	MMP9	hsa4318
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PARP1	hsa142
	Up-regulation	Expression	TIMP1	hsa7076
	Down-regulation	Expression	VEGFA	hsa7422
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	LNCaP	Prostate carcinoma	Homo sapiens (Human)	CVCL_0395
Result	EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
In Vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0428
Result	Combination of epigallocatechin-3-gallate and TRAIL synergistically increase the apoptosis and cleavage of procaspase-3 in pancreatic cancer cells

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B6B]	Nasopharyngeal carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BIRC5	hsa332
	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP8	hsa841
	Up-regulation	Activity	CASP9	hsa842
	Down-regulation	Expression	CDH13	hsa1012
	Down-regulation	Expression	CFLAR	hsa8837
	Down-regulation	Expression	FADD	hsa8772
	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	CNE-1	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_6889
	C666-1	Nasopharyngeal carcinoma	Homo sapiens (Human)	CVCL_7949
	NP69SV40T	Healthy	Homo sapiens (Human)	CVCL_F755
Result	EGCG sensitizes NPC cells to TRAIL-mediated apoptosis via modulation of extrinsic and intrinsic apoptotic pathways and inhibition of NF-κB activation.

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Expression	TNFRSF10A	hsa8797
In Vitro Model	A-375	Amelanotic melanoma	Homo sapiens (Human)	CVCL_0132
Result	EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	PEA15	hsa8682
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma

Pair Name	Epigallocatechin gallate, TNF-related apoptosis inducing ligand
Partner Name	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Expression	TNFRSF10B	hsa8795
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors

Pair Name	Epigallocatechin gallate, Gefitinib
Partner Name	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Inhibition-->Autophagy
Gene Regulation	Down-regulation	Expression	ATG5	hsa9474
	Down-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vivo Model	A549 cells were trypsinized, centrifuged, washed in PBS twice and injected s.c. (1×10⁶, 100 μL of PBS) into the left flanks of the 7–8-week-old mice (the animals were adapted to the lab environment for 7 days before experiments).
Result	EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Biological Phenomena	Induction-->Oxidative Stress
Gene Regulation	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	KB-A1	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_1D82
Result	These results demonstrate that the reversal effect of TP and EGCG on MDR acts, at least in part, regulating the doxorubicin induced intracellular concentration of ROS.

Pair Name	Epigallocatechin gallate, Osimertinib
Partner Name	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Inhibition-->Glycolysis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Activity	PRKAA1	hsa5562
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	NCI-H1975	Gefitinib-resistant lung adenocarcinoma	Homo sapiens (Human)	N.A.
In Vivo Model	Human NCI-H1975 or AR cells were subcutaneously inoculated into the right flank of nude mice at a density of 2×10⁶ cells for H1975 and 5×10⁶ cells for AR, respectively. When the tumors grew to reach around 100 cm3 in volume, the animals were randomly divided into 6 groups with equal size (n = 5 mice per group) for treatment.
Result	The combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells. The in vivo results obtained from mouse tumor xenograft model confirmed that EGCG effectively overcame osimertinib resistance.

Pair Name	Epigallocatechin gallate, Irinotecan
Partner Name	Irinotecan
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Biological Phenomena	Induction-->DNA damage
Gene Regulation	Down-regulation	Expression	CCNB1	hsa891
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Expression	CDK4	hsa1019
	Up-regulation	Expression	MAP1LC3A	hsa84557
	Up-regulation	Phosphorylation	RB1	hsa5925
	Down-regulation	Expression	TOP1	hsa7150
In Vitro Model	RKO	Colon carcinoma	Homo sapiens (Human)	CVCL_0504
	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
Result	EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells

Pair Name	Epigallocatechin gallate, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Immunogenic cell death
Gene Regulation	Down-regulation	Expression	ABCB1	hsa5243
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
	NCI-ADR-RES	High grade ovarian serous adenocarcinoma	Homo sapiens (Human)	CVCL_1452
In Vivo Model	About 1.0×10⁶ MCF-7/ADR cells were slowly injected into the subcutaneous region of male nude mice.
Result	PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

Pair Name	Green tea extract, Acetaminophen
Partner Name	Acetaminophen
In Vivo Model	Male B6C3F1 mice were provided by the US FDA National Center for Toxicological Research breeding colonies and all dosing was done at 8–9 weeks of age. Mice were fed National Institutes of Health (NIH)-41 irradiated diet ad libitum except during periods of fasting. Mice were fasted overnight for approximately 12 h before administration of APAP. In all studies, feed was given to the animals 4 h after the administration of APAP.
Result	GTE potentiated APAP-induced hepatotoxicity when administered after the APAP dose,

Pair Name	Epigallocatechin gallate, Bortezomib
Partner Name	Bortezomib
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
In Vivo Model	Four- to 6-week-old male athymic nu/nu mice were obtained from Harlan (Indianapolis, IN) and implanted subcutaneously with 5 × 106 RPMI/8226 multiple myeloma cells.
Result	(-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

Pair Name	Epigallocatechin gallate, Irinotecan
Partner Name	Irinotecan
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Biological Phenomena	Inhibition-->P-gp expression
In Vivo Model	Adult, male Sprague–Dawley rats (300 ± 20 g body weight) were provided by the Laboratory Animal Center at National Yang-Ming University, the rats were initially anaesthetized with urethane 1 g/mL and α-chloralose 0.1 g/mL (1 mL/kg, i.p.), and remained anaesthetized throughout the experimental period. The femoral vein was exposed for further drug administration.
Result	EGCG was found to inhibit the transport of CPT-11 and SN-38 into the biliary elimination and their half-lives in plasma could be substantially prolonged. Based on the food-drug interaction, persons taking daily nutritional supplements should be warned of this interaction possibility.