Table 3.

Molecular mechanisms by which extracts of saffron exert anti-cancer activity in GI cancers.

Type of Cancer	Secondary Metabolite	Mechanism of Action	Molecular Changes	References
Hepatic Cancer	crocin	Apoptosis	Down-regulation of hTERT gene Down-regulation of the expression of catalytic subunit of enzyme telomerase	[44,45,48]
		Anti-oxidant property and Anti-inflammatory effect	Increased the levels of GST, SOD, and CAT Reduced myeloperoxidase activity, malondialdehyde Inhibition of COX 2, iNOS, NF-κB
Pancreatic Cancer	crocetin	Cell cycle arrest at G2/M Phase	Reduced expression of Cdc-2 (hyperphosphoryltion) Reduced expression of Cdc-25c phosphatase Inhibition of Cyclin B1	[49]
	crocin, crocetin	Apoptosis	Increased expression of Bax protein Suppressed expression of Bcl-2 Elevated Bax/Bcl-2 ratio	[49,50,51]
	crocetin	Inhibition of cell proliferation	Reduced activity of EGFR Reduced phosphorylation of Akt	[49,51]
Colorectal Cancer	crocetin	Cell cycle arrest at S Phase	Reduced expression of cyclin A and cdk2	[52]
	crocin	Cell cycle arrest at G3 phase	Decrease in the levels of cyclin B1 and pH3	[42,45]
	Crocin, crocetin	Apoptosis	Augmented expression of p53 and P21	[42,53]
	crocin	DNA Damage	Up-regulation of H2AX	[42,45]
		Autophagolysis	Formation of LC3-II Decrease in protein levels of Beclin 1 and Atg 7 genes	[45]
Gastric Cancer	crocin	Apoptosis	Activation of caspases Elevated Bax/Bcl-2 ratio	[54]

GST: Glutathione S-transferases, SOD: Superoxide dismutase, CAT: Catalase, EGFR: Epidermal growth factor receptor.