Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP

Cancer Sci. 2011 Feb;102(2):468-71. doi: 10.1111/j.1349-7006.2010.01791.x. Epub 2010 Dec 7.

Abstract

Recently, we reported that combined ingestion of soy isoflavones and curcumin significantly decreased the serum level of prostate-specific antigen based on a randomized placebo-controlled double-blind clinical study. We investigated whether these polyphenols inhibited the proliferation of prostate cancer cells by activating a DNA damage response. The effects of isoflavones and curcumin on the expression and phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2AX variant (H2AX) and checkpoint kinase2 (Chk2) were examined in LNCaP cells. The induction of apoptosis in LNCaP cells was evaluated by poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the effects of a testosterone supplement on modulation of the DNA damage response were examined. Combined treatment of isoflavones and curcumin additively suppressed cellular proliferation and induced phosphorylation of ATM, histone H2AX, Chk2 and p53. Testosterone augmented the activation of the DNA damage response and PARP cleavage induced by curcumin. Our results indicate that activation of the DNA damage response by polyphenols might suppress the malignant transformation of prostate cancer. In addition, testosterone, when combined with curcumin, may have suppressive effects on the progression of prostate cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Checkpoint Kinase 2
  • Curcumin / pharmacology*
  • DNA Damage*
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Flavonoids
  • Histones / drug effects
  • Histones / metabolism
  • Humans
  • Immunoblotting
  • Isoflavones / pharmacology*
  • Male
  • Phenols
  • Poly(ADP-ribose) Polymerases / metabolism
  • Polyphenols
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / metabolism
  • Soybeans / chemistry
  • Testosterone / metabolism
  • Testosterone / pharmacology*
  • Tumor Suppressor Proteins / drug effects
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Flavonoids
  • H2AX protein, human
  • Histones
  • Isoflavones
  • Phenols
  • Polyphenols
  • Tumor Suppressor Proteins
  • Testosterone
  • Poly(ADP-ribose) Polymerases
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases
  • Curcumin