Pair Name	Crocin, Metformin
Partner Name	Metformin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Cell metastasis
Gene Regulation	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	4T1	Malignant neoplasms of the mouse mammary gland	Mus musculus (Mouse)	CVCL_0125
In Vivo Model	1×10⁶ 4T1 cells suspended in 0.2 ml phosphate-buffered saline and inoculated into the left dorsal flank regions of the mice.
Result	These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

Pair Name	Crocin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Inhibition-->Epithelial-mesenchymal transition
Gene Regulation	Up-regulation	Expression	FGFR3	hsa2261
In Vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens (Human)	CVCL_0139
In Vivo Model	Conducted subcutaneous tumorigenesis experiments in nude mice to evaluate the effects of crocin and DDP on the progression of GC xenografts in vivo.
Result	Our results showed that up-regulation of FGFR3 reversed the inhibitory effect of crocin+DDP on the MAPK/ERK signaling pathway. Still, this effect could be counteracted by PD184352, which simultaneously regulated the proliferation, apoptosis, and EMT of AGS cells. In conclusion, crocin, combined with DDP, inhibits proliferation, apoptosis, and EMT of GC through the FRFR3/MAPK/ERK pathway.

Pair Name	Crocin, Sorafenib
Partner Name	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	COX2	hsa4513
	Down-regulation	Expression	PARP1	hsa142
	Down-regulation	Expression	PCNA	hsa5111
	Down-regulation	Expression	RELA	hsa5970
In Vivo Model	Diethylnitrosamine was administered intraperitoneally to rats once a week for 15 weeks, leading to cirrhosis, and then 19 weeks later, leading to multifocal HCC. After 16 weeks of cancer induction, CR (200 mg/kg daily) and SB (10 mg/kg daily) were given orally to rats for three weeks, either separately or in combination.
Result	CR potentiates the suppressive effects of SB on tumor growth and provides the opportunity to strengthen the therapeutic effects of SB in the treatment of HCC.

Pair Name	Crocin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B66.0]	Oral squamous cell carcinoma		Investigative
Biological Phenomena	Induction-->Apoptosis
In Vitro Model	HN-5	Tongue squamous cell carcinoma	Homo sapiens (Human)	CVCL_8128
Result	Evaluation of apoptotic effect of crocin, cisplatin, and their combination in human oral squamous cell carcinoma cell line HN5

Pair Name	Crocin, Fluorouracil
Partner Name	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Expression	CCND1	hsa595
	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	PIK3CB	KEGG ID N.A.
In Vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_7254
In Vivo Model	Eight-week old female C57BL/6 mice were supplied by Pasteur Institute (Tehran, Iran) and divided into four groups (n = 6 each): control, treated with 5-FU, or crocin, or a 5-FU/crocin combination. Mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight followed by three cycles of 1.5% DSS in drinking water for 1 week and normal drinking water for 2 weeks.
Result	We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high-grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.