Geraniol, an acyclic dietary monoterpene, suppresses prostate cancer growth and enhances docetaxel chemosensitivity in cultured cell or xenograft tumor models. However, the mechanisms of the geraniol action against prostate cancer are largely unknown. In this study, we investigated the cellular and molecular mechanisms of geraniol-induced cell death in PC-3 prostate cancer cells. Among the examined structurally and functionally similar monoterpenes, geraniol potently induced apoptosis and autophagy. Although independent processes, apoptosis and autophagy acted as cooperative partners to elicit geraniol-induced cell death in PC-3 cells. At a molecular level, geraniol inhibited AKT signaling and activated AMPK signaling, resulting in mTOR inhibition. Combined treatment of AKT inhibitor and AMPK activator markedly suppressed cell growth compared to either treatment alone. Our findings provide insight into future investigations that are aimed at elucidating the role of apoptosis and autophagy in prostate cancer therapy and at developing anticancer strategies co-targeting AKT and AMPK.
Written by:
Kim SH, Park EJ, Lee CR, Chun JN, Cho NH, Kim IG, Lee S, Kim TW, Park HH, So I, Jeon JH. Are you the author?
Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Reference: Int J Oncol. 2011 Dec 23. Epub ahead of print.
doi: 10.3892/ijo.2011.1318
PubMed Abstract
PMID: 22200837
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