PEITC Inhibits Cholangiocarcinoma via Induction of Mitochondrial Dysfunction

Abstract

Phenethyl isothiocyanate (PEITC), a natural compound found abundantly in
cruciferous and other vegetables, has been shown to possess cancer chemopreventive activity.
The purpose of this investigation was to examine the cytotoxic effect of PEITC in
cholangiocarcinoma cells (CCA). Cholangiocarcinoma cells, KKU-100 and human liver
Chang cells used for comparison in the study. Effects of PEITC on cell growth and induction
of apoptosis was determined by fluorescent dye staining using acridine orange and ethidium
bromide. Cultured cells were exposed to PEITC for 3, 12, 24 and 48 hours following
assessment of cell viability and apoptotic cell death. PEITC can induce a large proportion of
cells to undergo apoptosis in a dose-time dependent manners. The PEITC induced depletion
of intracellular antioxidant GSH in the cell lines. Moreover, a rapid collapse of the
mitochondrial transmembrane potential, as measured by JC-1 staining, was observed
concurrently with an apparent apoptosis in both cells. Furthermore, Western blot analysis
were used to examine the antioxidant and survival response related proteins. The results
revealed that PEITC increased levels of Nrf2 and cyclin D1 in both cell lines, and Bax and
Trx protein expression was up-regulated in KKU-100. The effect of PEITC on cell growth
and apoptosis may contribute to cancer chemopreventive properties. In conclusion, our data
lucidly evidence the chemopreventive merits of dietary phytochemical PEITC in suppression
of cholangiocarcinoma.