Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells.
Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells.
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DOI：
10.3402/fnr.v60.30616
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发表时间：
2016
影响因子：
3.3
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Han X;Deng S;Wang N;Liu Y;Yang X
四氢姜黄素（Tetrahydrocurcumin， THC）是姜黄素的活性代谢产物，有报道称其具有与姜黄素相似的生物学效应，但其抗肿瘤活性的机制尚不清楚。采用MTT法、LDH法、流式细胞术、western blot法研究四氢大麻酚对人乳腺癌MCF-7细胞的抗肿瘤作用及其机制。四氢大麻酚对MCF-7细胞具有明显的细胞毒作用和抗增殖活性，且呈剂量依赖性，IC50为107.8 μM。流式细胞术分析显示，THC介导MCF-7细胞周期阻滞在G0/G1期，32.8%的MCF-7细胞在100 μM下24 h进入早期凋亡阶段。THC还通过线粒体途径剂量依赖性地导致MCF-7细胞凋亡，表现为caspase-3和caspase-9的激活，细胞内ROS升高，Bcl-2和PARP表达降低，Bax表达增加。同时，四氢大麻酚处理后细胞色素C被释放到细胞质中，线粒体膜电位丢失（Δψm）。四氢大麻酚是治疗乳腺癌化学预防药物的良好来源，作为抗肿瘤前体化合物具有很好的开发潜力。
Tetrahydrocurcumin (THC), an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF-7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 μM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 μM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Δψm) was observed after THC treatment. THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound.