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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.

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 micromol/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.

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  • Authors+Show Affiliations

    ,

    Department of Dermatology, University of Wisconsin, 1300 University Avenue, Medical Science Center B-25, Madison, WI 53706, USA.

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    Source

    Molecular cancer therapeutics 5:5 2006 May pg 1335-41

    MeSH

    Androgens
    Antineoplastic Agents, Phytogenic
    Apoptosis
    Carcinoma
    Cell Line, Tumor
    Cell Proliferation
    Cell Survival
    Dose-Response Relationship, Drug
    Down-Regulation
    Humans
    Male
    Microscopy, Fluorescence
    Phosphatidylinositol 3-Kinases
    Prostatic Neoplasms
    Proto-Oncogene Proteins c-akt
    Proto-Oncogene Proteins c-bcl-2
    Resveratrol
    Signal Transduction
    Stilbenes

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16731767

    Citation

    Aziz, Moammir H., et al. "Resveratrol-caused Apoptosis of Human Prostate Carcinoma LNCaP Cells Is Mediated Via Modulation of Phosphatidylinositol 3'-kinase/Akt Pathway and Bcl-2 Family Proteins." Molecular Cancer Therapeutics, vol. 5, no. 5, 2006, pp. 1335-41.
    Aziz MH, Nihal M, Fu VX, et al. Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Mol Cancer Ther. 2006;5(5):1335-41.
    Aziz, M. H., Nihal, M., Fu, V. X., Jarrard, D. F., & Ahmad, N. (2006). Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Molecular Cancer Therapeutics, 5(5), pp. 1335-41.
    Aziz MH, et al. Resveratrol-caused Apoptosis of Human Prostate Carcinoma LNCaP Cells Is Mediated Via Modulation of Phosphatidylinositol 3'-kinase/Akt Pathway and Bcl-2 Family Proteins. Mol Cancer Ther. 2006;5(5):1335-41. PubMed PMID: 16731767.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. AU - Aziz,Moammir H, AU - Nihal,Minakshi, AU - Fu,Vivian X, AU - Jarrard,David F, AU - Ahmad,Nihal, PY - 2006/5/30/pubmed PY - 2006/8/15/medline PY - 2006/5/30/entrez SP - 1335 EP - 41 JF - Molecular cancer therapeutics JO - Mol. Cancer Ther. VL - 5 IS - 5 N2 - 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 micromol/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. SN - 1535-7163 UR - https://www.unboundmedicine.com/medline/citation/16731767/Resveratrol_caused_apoptosis_of_human_prostate_carcinoma_LNCaP_cells_is_mediated_via_modulation_of_phosphatidylinositol_3'_kinase/Akt_pathway_and_Bcl_2_family_proteins_ L2 - http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16731767 DB - PRIME DP - Unbound Medicine ER -