Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB.

ABSTRACT: Death receptors of the tumor necrosis factor (TNF) receptor super family have been implicated in constitutive activation of nuclear factor-kappa B (NF-kappaB) in pancreatic cancer (PaC) cells. In this study, we demonstrate that fisetin, a natural flavonoid, induces apoptosis and inhibits invasion of chemoresistant PaC AsPC-1 cells through suppression of DR3-mediated NF-kappaB activation. Fisetin treatment resulted in dose-dependent inhibition of PaC cell growth and cell proliferation with concomitant induction of apoptosis. A cDNA array analysis revealed that fisetin modulates expression of more than 20 genes at transcription level with maximum decrease observed in DR3 expression and a parallel increase observed in the expression levels of IkappaBalpha, an NF-kappaB inhibitor. Down-regulat

SUBMITTER: Murtaza I 

PROVIDER: S-EPMC2944651 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature