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Research Articles: Therapeutics, Targets, and Development

Protein kinase CK2 modulates apoptosis induced by resveratrol and epigallocatechin-3-gallate in prostate cancer cells

¹ Cellular and Molecular Biochemistry Research Laboratory, Veterans Affairs Medical Center and ² Department of Laboratory Medicine and Pathology and ³ Cancer Center, University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Khalil Ahmed, Cellular and Molecular Biochemistry Research Laboratory (151), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417. Phone: 612-467-2594; Fax: 612-725-2093. E-mail: ahmedk{at}umn.edu

Abstract

Resveratrol and epigallocatechin-3-gallate (EGCG) are important candidates as chemopreventive agents by virtue of their ability to induce apoptosis in cancer cells. Casein kinase 2 (CK2) is a ubiquitous protein ser/thr kinase that plays diverse roles in cell proliferation and apoptosis. We have previously shown that overexpression of CK2 suppresses apoptosis induced by a variety of agents, whereas down-regulation of CK2 sensitizes cells to induction of apoptosis. We therefore investigated whether or not CK2 played a role in resveratrol and EGCG signaling in androgen-sensitive (ALVA-41) and androgen-insensitive (PC-3) prostate cancer cells. Resveratrol- and EGCG-induced apoptosis is associated with a significant down-regulation of CK2 activity and protein expression in both the ALVA-41 and PC-3 cells. Overexpression of CK2 protected prostatic cancer cells against resveratrol- and EGCG-induced apoptosis. Relatively low doses (10 µmol/L) of resveratrol and EGCG induced a modest proliferative response in cancer cells that could be switched to cell death by moderate inhibition of CK2. These findings characterize, for the first time, the effects of polyphenolic compounds on CK2 signaling in androgen-sensitive and androgen-insensitive prostatic carcinoma cells and suggest that resveratrol and EGCG may mediate their cellular activity, at least in part, via their targeting of CK2. Further, the data hint at the potential of using these polyphenols alongside CK2 inhibitors in combination chemotherapy. [Mol Cancer Ther 2007;6(3):1006–12]

Grant support: U.S. Department of Veterans Affairs Medical Research Fund and National Cancer Institute, Department of Health and Human Services USPHS research grant CA-15062.

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.

Received 8/14/06; revised 10/20/06; accepted 1/22/07.

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