Abstract 3669: Chemoprevention of mammary and prostate cancer by phenethyl isothiocyanate in vivo is associated with suppression of vimentin protein expression.

Abstract

Abstract Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables (eg, watercress), exhibits in vivo preventive efficacy against cancer in rodents induced by structurally diverse chemical carcinogens. We have also shown recently that dietary administration of PEITC (3 μmol PEITC/g diet) confers significant protection against breast and prostate cancer development in MMTV-neu and TRAMP model, respectively. Prevention of prostate cancer by PEITC administration in TRAMP mice was associated with induction of E-cadherin protein expression. Because suppression of E-cadherin protein level concomitant with induction of mesenchymal markers (eg, vimentin) is a biochemical hallmark of epithelial-mesenchymal transition, a process implicated in cancer metastasis, we hypothesized that PEITC treatment was likely to suppress vimentin protein expression. Contrary to this prediction, exposure of cultured human breast (MDA-MB-231) and prostate cancer cells (PC-3 and DU145) to PEITC resulted in a dose-dependent increase in vimentin protein level, which was observed as early as 6 hours post-treatment and persisted for the duration of the experiment (24 hours). RNA interference of vimentin resulted in a modest augmentation of PEITC-mediated inhibition of MDA-MB-231 and PC-3 cell migration as well as cell viability. Furthermore, the PEITC-induced apoptosis was moderately increased upon siRNA knockdown of vimentin protein level in MDA-MB-231 and PC-3 cells. To our surprise, PEITC administration caused a marked decrease in vimentin protein expression in vivo in tumors of MMTV-neu (breast) and TRAMP mice (prostate). The results of the present study indicate that cancer chemoprevention by PEITC in vivo is associated with suppression of vimentin protein expression. The present study was supported by the grant CA101753-09 awarded by the National Cancer Institute. Citation Format: Kozue Sakao, Eun-Ryeong Hahm, Shivendra V. Singh. Chemoprevention of mammary and prostate cancer by phenethyl isothiocyanate in vivo is associated with suppression of vimentin protein expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3669. doi:10.1158/1538-7445.AM2013-3669