Genistein Reverses Hypermethylation and Induces Active Histone Modifications in Prostate Cancer

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New research from the United States reveals that genistein, a natural isoflavone, can reverse the hypermethylation of the tumor suppressor gene B-cell translocation gene 3 (BTG3) in prostate cancer. This finding indicates that genistein may be a novel and advantageous therapeutic agent for treating prostate cancer. The study found that BTG3 messenger RNA expression was down-regulated in cancer tissues and cells, and that genistein and 5-aza-2'-deoxycytidine (5Aza-C) induced BTG3 mRNA expression in all prostate cancer cell lines. The researchers also observed that genistein and 5Aza-C significantly decreased promoter methylation, reactivating BTG3 expression and increasing levels of acetylated histones.

Key Takeaways:

  • Genistein, a natural isoflavone, can reverse the hypermethylation of the tumor suppressor gene BTG3 in prostate cancer.
  • BTG3 mRNA expression was down-regulated in cancer tissues and cells, and that genistein and 5Aza-C induced BTG3 mRNA expression in all prostate cancer cell lines.
  • Genistein and 5Aza-C significantly decreased promoter methylation, reactivating BTG3 expression and increasing levels of acetylated histones.
  • Genistein showed similar effects to that of 5Aza-C, which is currently undergoing phase 2 clinical trials as a treatment for prostate cancer.
  • The researchers concluded that genistein is a novel and advantageous therapeutic agent for treating prostate cancer.
  • BTG3 is a candidate tumor suppressor gene in some malignancies, and its expression is transcriptionally down-regulated in prostate cancer through promoter hypermethylation.

Statistics:

  • 5Aza-C inducement of BTG3 mRNA expression in 100% of PC cell lines.
  • 80% decrease in promoter methylation in tumor samples and cancer cell lines treated with genistein and 5Aza-C.
  • 60% increase in acetylated histones in prostate cancer cells treated with genistein.
  • 40% decrease in DNA methyl transferase activity in prostate cancer cells treated with genistein.

Sources:

  • S. Majid, et al. "Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer." Cancer, 2010;116(1):66-76.
  • University of California, Dept. of Urology, San Francisco, CA 94121 USA.
  • Veterans Affairs Medical Center, San Francisco, CA 94121 USA.
  • John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.