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Treatment with dibenzoxanthenes inhibits proliferation and induces apoptosis of HepG2 cells via the intrinsic mitochondrial pathway

机译:用二苯并毒素处理抑制增殖并通过内在的线粒体途径诱导HepG2细胞的凋亡

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摘要

Dibenzoxanthenes were reported to possess antitumor biological activity. In this study, we synthesized four dibenzoxanthenes analogs (4a-4d) with CN and COOCH3 groups, and revealed the underlying molecular biological mechanism. MTT assay indicated that compounds showed high cytotoxic activities against HepG2, HeLa, SGC-7901 and A549 cells. These compounds also caused DNA damage and G2/M phase arrest in HepG2 cells. Moreover, compounds induced cell apoptosis, which was associated with ROS generation, and a decrease of the mitochondrial membrane potential. Western blotting showed cytochrome c release, caspase-3 and caspase-9 activation, downregulation of Bcl-2, Bcl-xl and upregulation of Bax, Bid. Molecular location experiments showed that compounds 4a-4d entered the nuclei of cells. A cell scratch test and transwell assays indicated that compounds could suppress HepG2 cell migration and invasion. Taken together, our experiment results suggest that the four dibenzoxanthenes (4a-4d) exert their cytotoxicity on HepG2 cells by inducing ROS-mediated mitochondrial dysfunction apoptosis.
机译:据报道,二苯并毒剂具有抗肿瘤生物活性。在该研究中,通过CN和Cooch3组合成四种二苯并毒素类似物(4a-4d),并揭示了下面的分子生物机制。 MTT测定表明,化合物显示出对HepG2,Hela,SGC-7901和A549细胞的高细胞毒性活性。这些化合物还引起了HepG2细胞中的DNA损伤和G2 / M期阻滞。此外,化合物诱导细胞凋亡,与ROS产生相关,并降低线粒体膜电位。 Western Blotting显示细胞色素C释放,Caspase-3和Caspase-9激活,Bcl-2,Bcl-XL的下调和Bax,BID的上调。分子定位实验表明,化合物4a-4d进入细胞核。细胞划痕试验和Transwell测定表明,化合物可以抑制HepG2细胞迁移和侵袭。我们的实验结果表明,通过诱导ROS介导的线粒体功能障碍细胞凋亡,四种二苯并毒素(4A-4D)在HepG2细胞上施加细胞毒性。

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  • 来源
    《RSC Advances》 |2016年第76期|共12页
  • 作者单位

    Sun Yat Sen Univ Sch Chem &

    Chem Engn Guangzhou 510006 Guangdong Peoples R China;

    Guangdong Pharmaceut Univ Coll Pharm Guangzhou 510006 Guangdong Peoples R China;

    Guangdong Pharmaceut Univ Coll Pharm Guangzhou 510006 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Chem &

    Chem Engn Guangzhou 510006 Guangdong Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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