Phenethyl isothiocyanate inhibits the growth of androgen-dependent transplantable human prostate tumors that correlates with a decrease in CD31 a marker of tumor angiogenesis

A91

Phenethyl isothiocyanate (PEITC), which occurs naturally in certain cruciferous vegetables, has received considerable attention because of its ability to inhibit cytochrome P450s, induce apoptosis, and display antitumor activity in several types of cancer models, specifically prostate cancer. However, the angio-preventive effect of PEITC in vivo in androgen dependent prostate tumors remains largely unknown. This study examines the anticancer and angio-preventive effects of PEITC in androgen-dependent prostate cancer. In our xenograft model, we demonstrated that treatment of 3 µM PEITC in LNCap prostate cancer cells in vivo inhibited tumor growth. The inhibition in tumor growth was not associated with a decrease in cellular proliferation or induction of apoptosis, however, we were able to show that treatment of PEITC significantly inhibits platelet-endothelial cell adhesion molecule (PECAM-1), a marker for angiogenesis. In our in vitro studies LNCaP androgen-dependent prostate cancer cells reveal that treatment of PEITC did not inhibit prostate cancer cell growth. In addition, prostate cancer cell growth was not attributed to cell cycle arrest, however, it was associated with a reduction in mRNA levels of vascular endothelial growth factor (VEGF), a proangiogenic factor. These results reveal that PEITC may inhibit androgen-dependent prostate tumor growth by selectively targeting factors involve in the tumor microenvironment, suggesting that PEITC may be an important source for preventing angiogenesis in androgen-responsive prostate cancer. Moreover, PEITC may be an important therapeutic source for African American men who manifest aggressive prostate cancer and increase rates of recurrence.