PURPOSE: Treatment of androgen-independent metastatic prostate cancer with chemotherapeutic agent Estramustine showed diminishing success. Epidemiological studies showed an association between reduced cancer risk and dietary intake rich in phytochemicals from fruits and vegetables. We studied the molecular mechanisms through which phytochemicals muscadine grape skin extract (MSKE) and camalexin act individually, or in combination with Estramustine, to affect epithelial-mesenchymal transition (EMT), a process involved in prostate cancer progression. EMT can be induced by transcription factors such as Snail, and is associated with decrease in cell adhesion molecules like E-cadherin, and increase in mesenchymal markers such as vimentin. METHODOLOGY: MSKE, Camalexin, and Estramustine, were used in varying concentrations individually, and in combination, to conduct MTS proliferation assay on C4-2 and ARCaP prostate cancer EMT model overexpressing constitutively active Snail cDNA. EMT markers, E-cadherin and vimentin, were examined by Western Blot Analysis following treatments. RESULTS: MSKE or Camalexin with or without Estramustine significantly decreased cell proliferation of C4-2 cells. Surprisingly, ARCaP-Snail cells were more sensitive to MSKE and Estramustine treatments, and showed significant decrease in viability, as compared to control ARCaP-Neo cells. ARCaP-Snail cells treated with 5µg/ml MSKE showed a reversal in EMT as shown by increased E-cadherin and decreased vimentin levels. CONCLUSION: Both mono and combination treatments retarded prostate cancer cell proliferation and may show promise as a therapeutic agent to abrogate EMT and prostate cancer metastasis in the future. Supported by grants P20MD002285-01 & G12RR003062-22.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3384. doi:10.1158/1538-7445.AM2011-3384