Anthraquinone G503 induces apoptosis in gastric cancer cells through the mitochondrial pathway.
Anthraquinone G503 induces apoptosis in gastric cancer cells through the mitochondrial pathway.
复制标题
蒽醌 G503 通过线粒体途径诱导胃癌细胞凋亡
DOI：
10.1371/journal.pone.0108286
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Huang L;Zhang T;Li S;Duan J;Ye F;Li H;She Z;Gao G;Yang X
G503是从南海区中国红树林内生真菌的次生代谢产物中分离得到的一种蒽醌类化合物。本研究旨在阐明G503的抗肿瘤活性及其机制。对9个癌细胞系和2个正常细胞系进行的细胞活力测定表明，胃癌细胞系SGC7901是对G503最敏感的癌细胞。G503通过细胞凋亡诱导SGC7901细胞死亡。G503暴露可激活caspase-3、-8和-9。预先给予caspase抑制剂Z-VAD-FMK和caspase-9抑制剂Z-Lehd-FMK，但不用caspase-8抑制剂Z-IETD-FMK，可减弱G503的作用。这些结果表明，G503诱导的细胞凋亡主要是通过线粒体内部途径，而不是外在途径。G503还可使线粒体Bax/Bcl2比值升高，胞浆Bax/Bcl2比值降低。G503处理导致线粒体去极化，细胞色素c释放，随后caspase-9和caspase-3裂解。此外，据报道，G503还可能通过诱导Capase-4的裂解来激活内质网凋亡途径。考虑到G503对胃癌细胞有较低的50%抑制浓度，G503有望成为胃癌化疗的候选药物。
G503 is an anthraquinone compound isolated from the secondary metabolites of a mangrove endophytic fungus from the South China Sea. The present study elucidates the anti-tumor activity and the underlying mechanism of G503. Cell viability assay performed in nine cancer cell lines and two normal cell lines demonstrated that the gastric cancer cell line SGC7901 is the most G503-sensitive cancer cells. G503 induced SGC7901 cell death via apoptosis. G503 exposure activated caspases-3, -8 and -9. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK and caspase-9 inhibitor Z-LEHD-FMK, but not caspase-8 inbibitor Z-IETD-FMK, attenuated the effect of G503. These results suggested that the intrinsic mitochondrial apoptosis pathway, rather than the extrinsic pathway, was involved in G503-induced apoptosis. Furthermore, G503 increased the ratio of Bax to Bcl-2 in the mitochondria and decreased the ratio in the cytosol. G503 treatment resulted in mitochondrial depolarization, cytochrome c release and the subsequent cleavage of caspase -9 and -3. Moreover, it is reported that the endoplasmic reticulum apoptosis pathway may also be activated by G503 by inducing capase-4 cleavage. In consideration of the lower 50% inhibitory concentration for gastric cancer cells, G503 may serve as a promising candidate for gastric cancer chemotherapy.
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DOI：
10.1073/pnas.94.8.3668
发表时间：
1997-04-15
影响因子：
11.1
作者：
Hsu, YT;Wolter, KG;Youle, RJ
通讯作者：
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影响因子：
30.5
作者：
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影响因子：
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作者：
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