Pair Name	Hesperetin, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Down-regulation	Expression	ERBB2	hsa2064
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	RAC1	hsa5879
In Vitro Model	MCF-7/HER2-18	Invasive breast carcinoma	Homo sapiens (Human)	CVCL_0U80
Result	These results indicated that the combination of Hst and Dox-induced cell cycle arrest, apoptosis, decreased HER2, Rac1, MMP9 expression, and cell migration. Thus, Hst may have the potential to be developed as a co-chemotherapeutic agent combined with doxorubicin toward HER2 overexpressing breast cancer cells.

Pair Name	Hesperetin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	AIFM1	hsa9131
	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Expression	CCND1	hsa595
	Up-regulation	Expression	PTEN	hsa5728
In Vitro Model	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
	HGC-27	Gastric carcinoma	Homo sapiens (Human)	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens (Human)	CVCL_5334
	GES-1	Healthy	Homo sapiens (Human)	CVCL_EQ22
In Vivo Model	HGC-27 cells were suspended in 100 ul of PBS, and then implanted into the dorsal area, subcutaneously, of male BALB/c nude mice.
Result	Hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathway via upregulating PTEN expression, thereby significantly enhancing DDP's anti-tumor effect on GC

Pair Name	Hesperetin, Capecitabine
Partner Name	Capecitabine
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	IL4	hsa3565
	Up-regulation	Expression	IL4	hsa3565
	Down-regulation	Expression	MKI67	hsa4288
	Up-regulation	Expression	TP53	hsa7157
	Up-regulation	Expression	TP53	hsa7157
In Vivo Model	The current study was designed to evaluate the anti-carcinogenic effects of hesperetin (HES) alone and in combination with capecitabine (CAP) on 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. The rats were given DMH at 20 mg/kg body weight (b.w.)/week for 12 weeks and were orally treated with HES (25 mg/kg b.w.) and/or CAP (200 mg/kg b.w.) every other day for 8 weeks.
Result	It can be suggested that both HES and CAP, singly or in combination, have the potential to exert chemopreventive effects against DMH-induced colon carcinogenesis via the suppression of oxidative stress, the stimulation of the antioxidant defense system, the attenuation of inflammatory effects, the reduction in cell proliferation and the enhancement of apoptosis.

Pair Name	Hesperetin, Sorafenib
Partner Name	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	DNM1L	hsa10059
In Vivo Model	Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days.
Result	Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.