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Gossypol Induces Apoptosis by Activating p53 in Prostate Cancer Cells and Prostate Tumor-Initiating Cells

  1. Author:
    Volate, S. R.
    Kawasaki, B. T.
    Hurt, E. M.
    Milner, J. A.
    Kim, Y. S.
    White, J.
    Farrar, W. L.

  2. Author Address

    [Volate, Suresh R.; Kawasaki, Brian T.; Hurt, Elaine M.; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Milner, John A.; Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [White, Jeffrey] NCI, Off Canc Complementary & Alternat Med, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.;Volate, SR, NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21702 USA.;volatesr@mail.nih.gov farrar@mail.ncifcrf.gov
    1. Year: 2010
    2. Date: Feb
  2. Journal: Molecular Cancer Therapeutics
    1. 9
    2. 2
    3. Pages: 461-470
  4. Type of Article: Article
  5. ISSN: 1535-7163
  1. Abstract:

    Prostate cancer continues to represent a burgeoning medical problem in the United States. Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer. The current studies were undertaken to examine the chemotherapeutic efficacy of gossypol on human prostate cancer cell lines and prostate tumor-initiating cells. Gossypol reduced the viability of three prostate cancer cell lines (LAPC4, PC3, and DU145) with an IC50 between 3 and 5 mu mol/L. Additionally, gossypol was effective at inhibiting prostate tumor-initiating cell-driven tumor growth in a nonobese diabetic/severe combined immunodeficient xenograft model. Our integrated molecular profiling approach encompassing proteomics, activated transcription factors, and genomics suggests that the decrease in viability was associated with increased DNA damage and the induction of apoptosis. Exposure of DU145 cells to gossypol (1-10 mu mol/L) resulted in the activation of 13 proteins and 7 transcription factors, and the expression of 17 genes involved in the mitochondrial pathway of apoptosis. These studies show for the first time that gossypol treatment induces DNA damage and activates p53. Collectively, these data support the use of gossypol as a novel agent for prostate cancer. Mol Cancer Ther; 9(2); 461-70. (C) 2010 AACR.

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External Sources

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  2. DOI: 10.1158/1535-7163.mct-09-0507
  3. View record in Web of Science®
  4. WOS: 000278487200021

Library Notes

  1. Fiscal Year: FY2009-2010
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