3,3′-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells
3,3′-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells
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DOI：
10.1016/j.taap.2012.07.007
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发表时间：
2012-09-15
影响因子：
3.8
通讯作者：
Ho, Emily
中科院分区：
文献类型：
--
作者：
Beaver, Laura M.;Yu, Tian-Wei;Ho, Emily
增加十字花科蔬菜的消费量与降低患前列腺癌的风险有关。吲哚-3-甲醇（I3 C）和3，3 '-二吲哚基甲烷（DIM）是来自十字花科蔬菜的植物化学物质，在实验模型中显示出抑制前列腺癌的前景。组蛋白去乙酰化酶（HDAC）抑制是癌症预防和治疗的新兴靶点。我们试图检查I3 C和DIM对人前列腺癌细胞系中HDAC的影响：雄激素不敏感的PC-3细胞和雄激素敏感的LNCaP细胞。I3 C适度抑制LNCaP细胞中的HDAC活性25%，但在PC-3细胞中未检测到HDAC活性的抑制。相比之下，DIM显着抑制HDAC活性在两个细胞系高达66%。HDAC活性的降低与p21表达的增加相关，p21是HDAC抑制剂的已知靶点。DIM处理引起两种癌细胞系中HDAC 2蛋白表达的显著降低，但未检测到HDAC 1、HDAC 3、HDAC 4、HDAC 6或HDAC 8的蛋白水平的显著变化。总之，这些结果表明，DIM对HDAC活性的抑制可能有助于植物化学物质在前列腺中的抗增殖作用。DIM靶向异常表观遗传模式的能力，以及其对致癌物解毒的作用，可能使其成为一种有效的化学预防剂，靶向前列腺癌发生的多个阶段。爱思唯尔公司出版
Increased consumption of cruciferous vegetables is associated with a reduced risk of developing prostate cancer. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are phytochemicals derived from cruciferous vegetables that have shown promise in inhibiting prostate cancer in experimental models. Histone deacetylase (HDAC) inhibition is an emerging target for cancer prevention and therapy. We sought to examine the effects of I3C and DIM on HDACs in human prostate cancer cell lines: androgen insensitive PC-3 cells and androgen sensitive LNCaP cells. I3C modestly inhibited HDAC activity in LNCaP cells by 25% but no inhibition of HDAC activity was detected in PC-3 cells. In contrast, DIM significantly inhibited HDAC activity in both cell lines by as much as 66%. Decreases in HDAC activity correlated with increased expression of p21, a known target of HDAC inhibitors. DIM treatment caused a significant decrease in the expression of HDAC2 protein in both cancer cell lines but no significant change in the protein levels of HDAC1, HDAC3, HDAC4, HDAC6 or HDAC8 was detected. Taken together, these results show that inhibition of HDAC activity by DIM may contribute to the phytochemicals' anti-proliferative effects in the prostate. The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification of carcinogens, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis. Published by Elsevier Inc.