Pulmonary , gastrointestinal and urogenital pharmacology Physcion induces mitochondria-driven apoptosis in colorectal cancer cells via downregulating EMMPRIN
Pulmonary , gastrointestinal and urogenital pharmacology Physcion induces mitochondria-driven apoptosis in colorectal cancer cells via downregulating EMMPRIN
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发表时间：
2015
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通讯作者：
Xue-hong Chen;Hui Gao;Yan-tao Han;Junli Ye;Jing Xie;Chunbo Wang
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作者：
Xue-hong Chen;Hui Gao;Yan-tao Han;Junli Ye;Jing Xie;Chunbo Wang
大黄素甲醚是一种从陆地和海洋中广泛分离和表征的蒽醌类化合物，对多种肿瘤细胞具有抗肿瘤作用，主要通过抑制细胞增殖、诱导细胞凋亡和细胞周期停滞等途径发挥作用。然而，人们对其在肿瘤进展中的作用机制知之甚少。在本研究中，我们研究了大黄素甲素诱导人结直肠癌(CRC)细胞株HCT116凋亡的分子机制。我们的结果表明，大黄素甲素以剂量和时间依赖的方式抑制肿瘤细胞的存活，并通过内源性线粒体途径诱导细胞凋亡。我们的结果还表明，大黄素甲素处理显著抑制HCT116细胞的细胞外基质金属蛋白酶诱导物(EMMPRIN)的表达，并呈剂量依赖关系，过表达EMMPRIN蛋白显著减少大黄素甲素诱导的细胞凋亡。此外，我们的结果进一步表明，大黄素甲素对EMMPRIN的调节作用与AMPK/缺氧诱导因子1α(HIF-1α)信号通路有关。本研究首次提供了大黄素甲素通过AMPK/HIF-1α信号通路下调EMMPRIN诱导大肠癌细胞线粒体凋亡的实验证据，并为其抗肿瘤作用提供了新的机制。2015年由爱思唯尔出版公司出版。
Physcion, an anthraquinone derivative widely isolated and characterized from both terrestrial and marine sources, has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, little is known about the mechanisms underlying its role in tumor progression. In the present study, we investigated the molecular mechanisms involved in physcion-induced apoptosis in human colorectal cancer (CRC) lines HCT116. Our results showed that physcion inhibited tumor cell viability in a doseand time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway. Our results also revealed that physcion treatment significantly inhibited extracelluar matrix metalloproteinase inducer (EMMPRIN) expression in HCT116 cells in a dose-dependent manner and overexpression of EMMPRIN protein markedly reduced physcioninduced cell apoptosis. Furthermore, our results strongly indicated the modulating effect of physcion on EMMPRIN is correlated with AMP-activated protein kinase (AMPK)/Hypoxia-inducible factor 1α (HIF-1α) signaling pathway. Our data provide the first experimental evidence that physcion induces mitochondrial apoptosis in CRC cells by downregulating of EMMPRIN via AMPK/HIF-1α signaling pathway and suggest a new mechanism to explain its anti-tumor effects. & 2015 Published by Elsevier B.V.