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Research Articles: Therapeutics, Targets, and Development

Enterolactone induces apoptosis in human prostate carcinoma LNCaP cells via a mitochondrial-mediated, caspase-dependent pathway

¹ Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Shanghai, China; and ² School of Nursing and Department of Surgery, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Xu Lin, Institute for Nutritional Sciences, 294 Tai Yuan Rd., Shanghai 200031, China. Phone: 86-21-5492-0249; Fax: 86-21-5492-0291. E-mail: xlin{at}sibs.ac.cn

Abstract

The mammalian lignan enterolactone is a major metabolite of plant-based lignans that has been shown to inhibit the growth and development of prostate cancer. However, little is known about the mechanistic basis for its anticancer activity. In this study, we report that enterolactone selectively suppresses the growth of LNCaP prostate cancer cells by triggering apoptosis. Mechanistic studies showed that enterolactone-induced apoptosis was characterized by a dose-dependent loss of mitochondrial membrane potential, release of cytochrome c and cleavage of procaspase-3 and poly(ADP-ribose)-polymerase (PARP). Caspase dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate enterolactone-mediated apoptosis. Mechanistic studies suggested roles for Akt, GSK-3ß, MDM2, and p53 in enterolactone-dependent apoptosis. Our findings encourage further studies of enterolactone as a promising chemopreventive agent against prostate cancer. [Mol Cancer Ther 2007;6(9):2581–90]

Grant support: National Natural Science Foundation of China (Grant 30371209), the Innovation Direction Projects of the Chinese Academy of Sciences (KSCX2-2-25), Science and Technology Commission of Shanghai Municipality (Grant 04DZ14007), and the National Cancer Institute (R01 CA85740).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

³ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 3/29/07; revised 6/ 7/07; accepted 7/18/07.

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