Isorhamnetin suppresses PANC-1 pancreatic cancer cell proliferation through S phase arrest

Isorhamnetin, a flavonoid ingredient derived from Vernonia anthelmintica (L.) Willd., has shown a spectrum of antitumor activity. However, the chemopreventive potential of isorhamnetin on advanced pancreatic cancer and the underlying molecular mechanism remain unknown. In the current study, treatment of the advanced pancreatic adenocarcinoma cell line PANC-1 with isorhamnetin resulted in robust cell growth arrest. PI-annexin V double staining and Hoechst 33258 staining revealed that isorhamnetin moderately induced early apoptosis without morphological alterations of nuclei. Instead, isorhamnetin caused cell cycle S-phase arrest through downregulation of cyclin A. In addition, isorhamnetin decreased the phosphorylation levels of MEK and ERK in the Ras/MAPK pathway, which is involved in regulating cell proliferation, differentiation and apoptosis. Wound-healing experiments demonstrated isorhamnetin significantly reduced the migratory behavior of PANC-1 cells. Altogether, the present study suggests that isorhamnetin may be a potential agent for prevention of pancreatic carcinoma.