title: In vitro and in vivo effects of phenethyl isothiocyanate treatment on vimentin protein expression in cancer cells.
abstract: We have shown previously that cancer prevention by cruciferous vegetable constituent phenethyl isothiocyanate (PEITC) in a transgenic mouse model of prostate cancer is associated with induction of E-cadherin protein expression. Because suppression of E-cadherin protein concomitant with induction of mesenchymal markers (e.g., 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 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 h posttreatment and persisted for the duration of the experiment (24 h). 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 in MDA-MB-231 and PC-3 cells. To our surprise, PEITC treatment caused a marked decrease in vimentin protein expression in breast and prostate carcinoma in vivo in transgenic mouse models, although the difference was statistically significant only in the breast carcinomas. The present study highlights the importance of in vivo correlative studies for validation of the in vitro mechanistic observations.
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Kozue
authors.initials: K
authors.lastname: Sakao
authors.forename: Eun-Ryeong
authors.initials: ER
authors.lastname: Hahm
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D034741:RNA, Small Interfering; D014746:Vimentin; C058305:phenethyl isothiocyanate