Abstract
Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.
Highlights
Digestive cancers are major causes of cancer mortality and morbidity in the world [1]
The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through activation of CDKN1A, Semaphorin 3E (SEMA3E), GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes
The human liver cancer cells (HepG-2, IC50: 3.2μM) were more sensitive to fisetin effect compared to colorectal (Caco-2, IC50: 16.4 μM) and pancreatic cancer cells (Suit-2, IC50: 8.1μM)
Summary
Digestive cancers are major causes of cancer mortality and morbidity in the world [1]. Gastrointestinal cancers include malignancies arising in the esophagus, gallbladder, pancreas, liver and bile ducts, small intestine, stomach, colon and rectum. The incidence and mortality rates of these tumors differ significantly. One-fifth of the cancer incidence and nearly one-fourth of the cancer related deaths in the US were due to gastrointestinal cancers. Colorectal and gastric cancers are the most common gastrointestinal cancers all over the world [2]. The 5-year survival is 90% and 63%, respectively, when these malignancies are detected
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