Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29
Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29
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DOI：
10.1006/excr.2001.5285
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发表时间：
2001-08-15
影响因子：
3.7
通讯作者：
Ogier-Denis, E
中科院分区：
文献类型：
--
作者：
Bauvy, C;Gane, P;Ogier-Denis, E
自噬是一个主要的分解代谢过程，允许细胞内细胞器的更新，细胞通过这些细胞器维持自身的动态平衡。我们以前已经证明自噬是由两条转导通路控制的，在人类结肠癌细胞株HT-29中，自噬是由异源三聚体Gi3蛋白和磷脂酰肌醇3-激酶活性介导的。在这里，我们发现3-甲基腺嘌呤，一种自噬的抑制剂，增加了HT-29细胞对舒林酸硫化物诱导的凋亡的敏感性，舒林酸硫化物是一种抑制环氧合酶的非类固醇抗炎药物。类似地，高表达G(αi3)蛋白的GTPase缺陷突变体(Q204L)的HT-29细胞自噬比率较低，比亲代的HT-29细胞对硫化物诱导的细胞凋亡更敏感。在两种细胞群中，我们没有观察到COX-2、Bcl2、BclXL、Bax和Akt/PKB活性的表达模式的差异。然而，Q204L过表达细胞的细胞色素c释放率高于HT-29细胞。这些结果表明，自噬可以通过隔离线粒体促死亡因子，如细胞色素c.(C)2001学术出版社来延缓结肠癌细胞的凋亡。
Autophagy is a major catabolic process allowing the renewal of intracellular organelles by which cells maintain their homeostasis. We have previously shown that autophagy is controlled by two transduction pathways mediated by a heterotrimeric Gi3 protein and phosphatidylinositol 3-kinase activities in the human colon cancer cell line HT-29. Here, we show that 3-methyladenine, an inhibitor of autophagy, increases the sensitivity of HT-29 cells to apoptosis induced by sulindac sulfide, a nonsteroidal anti-inflammatory drug which inhibits the cyclooxygenases. Similarly, HT-29 cells overexpressing a GTPase-deficient mutant of the G(alpha i3) protein (Q204L), which have a low rate of autophagy, were more sensitive to sulindac sulfide-induced apoptosis than parental HT-29 cells. In both cell populations we did not observe differences in the expression patterns of COX-2, Bcl-2, Bcl(XL), Bax, and Akt/PKB activity. However, the rate of cytochrome c release was higher in Q204L-overexpressing cells than in HT-29 cells. These results suggest that autophagy could retard apoptosis in colon cancer cells by sequestering mitochondrial death-promoting factors such as cytochrome c. (C) 2001 Academic Press.