Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29 |
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Authors: | Bauvy C Gane P Arico S Codogno P Ogier-Denis E |
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Affiliation: | INSERM U504 Glycobiologie et Signalisation Cellulaire, 16, Avenue Paul-Vaillant Couturier, 94807 Villejuif Cedex, France. |
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Abstract: | 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. |
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Keywords: | autophagy apoptosis colon cancer nonsteroidal anti-inflammatory drug sulindac sulfide programmed cell death mitochondria cytochrome c caspase |
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