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Oleanane Triterpenoid CDDO‐Me inhibits growth and induces apoptosis in prostate cancer cells by independently targeting pro‐survival Akt and mTOR by Dorrah Deeb; Xiaohua Gao; Hao Jiang; Scott A. Dulchavsky; Subhash C. Gautam is a Medicine article available to read on EtoBox.

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## Abstract ## BACKGROUND Synthetic triterpenoids are potent anticancer agents, but their therapeutic efficacy or mechanism of action for prostate cancer has not been investigated. The goal of this study was to determine the antitumor activity and the mechanism of action of methyl‐2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oate (CDDO‐Me), a oleanane‐derived synthetic triterpenoid for human prostate cancer cells. ## METHODS The antitumor activity of CDDO‐Me for hormone‐refractory PC‐3 (AR^−^) and C4‐2 (AR^+^) prostate cancer cell lines was determined by effects on cell growth and induction of apoptosis, identification of molecular targets, and therapeutic efficacy in vivo in PC‐3 xenograft model. ## RESULTS CDDO‐Me inhibited the growth and induced apoptosis in PC‐3 and C4‐2 cells at extremely low concentrations. The antitumor activity of CDDO‐Me was associated with the inhibition of p‐Akt, mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF‐κB) signaling proteins and their downstream targets such as p‐Bad and p‐Foxo3a (Akt); p‐S6K1, p‐eIF‐4E and p‐4E‐BP1 (mTOR); and COX‐2, VEGF and cyclin D1(NF‐κB). Silencing of Akt sensitized the PC‐3 cells to CDDO‐Me, whereas overex

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Author

Dorrah Deeb; Xiaohua Gao; Hao Jiang; Scott A. Dulchavsky; Subhash C. Gautam

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0270-4137)

Published

2009

Language

EN

Field

Medicine (Health Sciences)