Phenethyl isothiocyanate (
PEITC), an
isothiocyanate abundantly found in cruciferous vegetables have been shown to induce apoptosis through MAPK pathway in prostate and
colon cancer cells. In the present study, we investigate the effect of
PEITC on cell cycle regulation of HT-29
colon cancer cells. Using flow cytometry and Western blot analyses, we found that
PEITC significantly induced G1 cell cycle arrest in HT-29 cells. We showed that the cell cycle arrest was not related to
beta-catenin translocation into the nucleus. Interestingly, inhibition of p38 attenuated the cell cycle arrest, suggesting that cell cycle arrest by
PEITC was caused by the activation of MAPK pathway. Treatments of
PEITC resulted in a dose-dependent down-regulation of
cyclins A, D, E and pRb
protein expression. The down-regulation can be attributed to the activation of the p38 pathway, since inhibition of its activities by specific inhibitor blocked
PEITC's ability to decrease the expression level of
cyclins A and D and attenuate cell cycle arrest effect of
PEITC. In conclusion, this study shows for the first time that
PEITC can arrest HT-29 cells in G1 phase by down-regulation of
cyclins through the activation of
p38 MAPK signaling pathway.