Abstract 822: Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane

Abstract

Abstract Chemopreventive efficacy of D,L-sulforaphane (SFN) against prostate cancer has been shown in a transgenic mouse model but the underlying mechanism is not fully understood. The present study demonstrates that c-Myc, which is an oncogenic transcription factor frequently upregulated in human prostate cancer, is a molecular target of SFN. Exposure of human prostate cancer cells (LNCaP, C4-2, and PC-3) and a cell line derived from prostate adenocarcinoma of a transgenic mouse (Myc-CaP) to SFN resulted in a marked decrease in c-Myc protein level. Naturally-occurring thio, sulfinyl, and sulfonyl analogues of SFN were also effective in causing suppression of c-Myc protein level. The c-Myc is a known regulator of cellular metabolism but basal glycolysis was not altered by SFN treatment in empty vector transfected or in c-Myc overexpressing PC-3 cells. The effect of SFN treatment on prostate cancer stem-like cells (pCSC) was also determined as c-Myc is implicated in their maintenance. Analysis of aldehyde dehydrogenase 1 activity, CD49f+ fraction, and sphere forming efficiency revealed dose-dependent inhibition of pCSC in SFN-treated cells. The pCSC inhibition by SFN was partially but significantly attenuated by overexpression of c-Myc. Expression profiling revealed upregulation of a set of stemness genes by c-Myc overexpression but their downregulation by SFN treatment. Finally, oral administration of SFN to Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice resulted in a marked decrease in c-Myc protein expression in the adenocarcinoma. In conclusion, this study indicates that c-Myc downregulation contributes to pCSC inhibition by SFN. This investigation was supported by grant CA115498 awarded by the National Cancer Institute. Citation Format: Su-Hyeong Kim, Avani R. Vyas, Shivendra V. Singh. Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 822.