Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
Cancer Sci. 2011 Feb;102(2):468-71. doi: 10.1111/j.1349-7006.2010.01791.x. Epub 2010 Dec 7.
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.
最近，我们在一项随机安慰剂对照双盲临床试验中报告称，大豆异黄酮和姜黄素联合摄入可显著降低前列腺特异性抗原的血清水平。我们研究了这些多酚是否通过激活 DNA 损伤反应来抑制前列腺癌细胞的增殖。在 LNCaP 细胞中，检测了异黄酮和姜黄素对共济失调毛细血管扩张突变激酶 (ATM)、组蛋白 H2AX 变体 (H2AX) 和检查点激酶 2 (Chk2) 的表达和磷酸化的影响。通过多聚（ADP-核糖）聚合酶 (PARP) 切割评估 LNCaP 细胞中的细胞凋亡诱导。此外，还研究了睾酮补充对 DNA 损伤反应调节的影响。异黄酮和姜黄素的联合处理可相加抑制细胞增殖，并诱导 ATM、组蛋白 H2AX、Chk2 和 p53 的磷酸化。睾酮增强了姜黄素诱导的 DNA 损伤反应的激活和 PARP 切割。我们的结果表明，多酚激活 DNA 损伤反应可能抑制前列腺癌的恶性转化。此外，当与姜黄素联合使用时，睾酮可能对前列腺癌的进展具有抑制作用。
