Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP.
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.
Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
Hisamitsu
H
Ide
Jingsong
J
Yu
Yan
Y
Lu
Toshiyuki
T
China
Tomoka
T
Kumamoto
Tatsuro
T
Koseki
Satoru
S
Muto
Shigeo
S
Horie
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D064447:Checkpoint Kinase 2; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D010636:Phenols; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D059808:Polyphenols; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005419:Flavonoids; C468783:H2AX protein, human; D006657:Histones; D007529:Isoflavones; D010636:Phenols; D059808:Polyphenols; D025521:Tumor Suppressor Proteins; D013739:Testosterone; D011065:Poly(ADP-ribose) Polymerases; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D003474:Curcumin