title: Nutrient availability alters the effect of autophagy on sulindac sulfide-induced colon cancer cell apoptosis.
abstract: Autophagy is a catabolic process by which a cell degrades its intracellular materials to replenish itself. Induction of autophagy under various cellular stress stimuli can lead to either cell survival or cell death via apoptotic and/or autophagic (nonapoptotic) pathways. The NSAID sulindac sulfide induces apoptosis in colon cancer cells. Here, we show that inhibition of autophagy under serum-deprived conditions resulted in significant reductions of sulindac sulfide-induced apoptosis in HT-29 colon cancer cells. In contrast, inhibition of autophagy under conditions where serum is available significantly increased sulindac sulfide-induced apoptosis in HT-29 cells. We previously showed that the apoptosis inhibitor, survivin, plays a role in regulating NSAID-induced apoptosis and autophagic cell death. Here, we show that survivin protein half-life is increased in the presence of autophagy inhibitors under serum-deprived conditions, but not under conditions when serum is available. Thus, the increased levels of survivin may be a factor contributing to inhibition of sulindac sulfide-induced apoptosis under serum-deprived conditions. These results suggest that whether a cell lives or dies due to autophagy induction depends on the balance of factors that regulate both autophagic and apoptotic processes.
authors: Research Division, Veterans Affairs Medical Center, 5901 E 7th Street, Long Beach, CA 90822, USA ; Department of Medicine, University of California, 101 The City Drive, Irvine, Orange, CA 92868, USA.
authors: Shiun-Kwei
authors: SK
authors: Chiou
authors: Neil
authors: N
authors: Hoa
authors: Lisheng
authors: L
authors: Ge
authors: Martin R
authors: MR
authors: Jadus