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Molecular Cancer Therapeutics
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Research Articles: Therapeutics

Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins

Moammir H. Aziz, Minakshi Nihal, Vivian X. Fu, David F. Jarrard and Nihal Ahmad
Moammir H. Aziz
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Minakshi Nihal
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Vivian X. Fu
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David F. Jarrard
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Nihal Ahmad
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DOI: 10.1158/1535-7163.MCT-05-0526 Published May 2006
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Abstract

Prostate cancer is a major health problem in the U.S. and the available treatment and surgical options have proven to be inadequate in controlling the mortality and morbidity associated with this disease. It is therefore necessary to intensify our efforts to better understand this disease and develop novel approaches for its prevention and treatment. This study was conducted to evaluate the chemopreventive/antiproliferative potential of resveratrol (trans-3,4′,5,-trihydroxystilbene) against prostate cancer and its mechanism of action. Treatment with resveratrol (0–50 μmol/L for 24 hours) resulted in a significant (a) decrease in cell viability, (b) decrease of clonogenic cell survival, (c) inhibition of androgen (R1881)-stimulated growth, and (d) induction of apoptosis in androgen-responsive human prostate carcinoma (LNCaP) cells. Interestingly, at similar concentrations, resveratrol treatment did not affect the viability or rate of apoptosis in normal human prostate epithelial cells. Furthermore, our data showed that resveratrol-treatment resulted in significant dose-dependent inhibition in the constitutive expression of phosphatidylinositol 3′-kinase and phosphorylated (active) Akt in LNCaP cells. Resveratrol treatment for LNCaP cells was also found to result in a significant (a) loss of mitochondrial membrane potential, (b) inhibition in the protein level of antiapoptotic Bcl-2, and (c) increase in proapoptotic members of the Bcl-2 family, i.e., Bax, Bak, Bid, and Bad. Taken together, our data suggested that resveratrol causes an inhibition of phosphatidylinositol 3′-kinase/Akt activation that, in turn, results in modulations in Bcl-2 family proteins in such a way that the apoptosis of LNCaP cells is promoted. Based on these studies, we suggest that resveratrol could be developed as an agent for the management of prostate cancer. [Mol Cancer Ther 2006;5(5):1335–41]

Keywords:
  • Resveratrol
  • Prostate cancer
  • PI3K
  • Akt
  • Bcl-2

Footnotes

  • 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.

    • Accepted March 24, 2006.
    • Received December 15, 2005.
    • Revision received March 7, 2006.
  • American Association for Cancer Research
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Molecular Cancer Therapeutics: 5 (5)
May 2006
Volume 5, Issue 5
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Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins
Moammir H. Aziz, Minakshi Nihal, Vivian X. Fu, David F. Jarrard and Nihal Ahmad
Mol Cancer Ther May 1 2006 (5) (5) 1335-1341; DOI: 10.1158/1535-7163.MCT-05-0526

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Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3′-kinase/Akt pathway and Bcl-2 family proteins
Moammir H. Aziz, Minakshi Nihal, Vivian X. Fu, David F. Jarrard and Nihal Ahmad
Mol Cancer Ther May 1 2006 (5) (5) 1335-1341; DOI: 10.1158/1535-7163.MCT-05-0526
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Molecular Cancer Therapeutics
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