Shikonin causes apoptosis by disrupting intracellular calcium homeostasis and mitochondrial function in human hepatoma cells

文献类型： 外文期刊

第一作者： Wang, Hui

作者： Wang, Hui;Liu, Zheng;Wu, Handong;Li, Xiangchen;Zhao, Ruijie;Pu, Yabin;Guan, Weijun

作者机构：

关键词： human hepatocellular carcinoma;tumorigenesis;DNA damage;cell cycle progression;mitochondrial function

期刊名称：EXPERIMENTAL AND THERAPEUTIC MEDICINE （ 影响因子：2.447； 五年影响因子：2.263 ）

ISSN： 1792-0981

年卷期： 2018 年 15 卷 2 期

页码：

收录情况： SCI

摘要： Shikonin is known to suppress proliferation and induce apoptosis in a variety of cancer cell lines. In the present study, SMMC-7721 human hepatocellular carcinoma cells were treated with shikonin (1, 2 or 4 mu M) for 12-48 h. Cell morphological alterations and DNA damage were determined. Furthermore, changes in cell cycle, mitochondrial transmembrane potential, calcium homeostasis and levels of reactive oxygen species were measured. Shikonin-treated SMMC-7721 cells exhibited morphological changes and DNA damage. Shikonin inhibited cell proliferation causing cell cycle arrest at the G(0)/G(1) phase and induced apoptosis in a dose- and time-dependent manner. Shikonin-induced apoptosis was associated with activation of caspases-3, -8 and -9, elevated levels of intracellular Ca2+ and reactive oxygen species, reduced mitochondrial membrane potential and enhanced efflux of Ca2+ and K+. Gene expression B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), p53 and caspase-3 was up-regulated, whereas Bcl-2 expression was downregulated. Shikonin caused apoptosis by inhibiting cell cycle progression, disrupting Ca2+ homeostasis, inducing oxidative stress and triggering mitochondrial dysfunction. Activation of caspases-3, -8 and -9, K+ efflux, and regulation of Bax, Bcl-2, p53 and caspase-3 expression are involved in the process. These results provide in-depth insight into the mechanisms of action of shikonin in the treatment of cancer.

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