Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy
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Recently, the interest in natural products for the treatment ofcancer is increasing because they are the pre-screenedcandidates. In the present study, we demonstrate the therapeuticeffect of celastrol, a triterpene extracted from the rootbark of Chinese medicine on gastric cancer. The proliferationof AGS and YCC-2 cells were most sensitively decreased in sixkinds of gastric cancer cell lines after the treatment withcelastrol. Celastrol inhibited the cell migration and increasedG1 arrest in cell-cycle populations in both cell lines. Thetreatment with celastrol significantly induced autophagy andapoptosis and increased the expression of autophagy andapoptosis-related proteins. We also found an increase inphosphorylated AMPK following a decrease in all phosphorylatedforms of AKT, mTOR and S6K after the treatmentwith celastrol. Moreover, gastric tumor burdens were reducedin a dose-dependent manner by celastrol administration in axenografted mice model. Taken together, celastrol distinctlyinhibits the gastric cancer cell proliferation and induces autophagyand apoptosis.
Abstract
Recently, the interest in natural products for the treatment ofcancer is increasing because they are the pre-screenedcandidates. In the present study, we demonstrate the therapeuticeffect of celastrol, a triterpene extracted from the rootbark of Chinese medicine on gastric cancer. The proliferationof AGS and YCC-2 cells were most sensitively decreased in sixkinds of gastric cancer cell lines after the treatment withcelastrol. Celastrol inhibited the cell migration and increasedG1 arrest in cell-cycle populations in both cell lines. Thetreatment with celastrol significantly induced autophagy andapoptosis and increased the expression of autophagy andapoptosis-related proteins. We also found an increase inphosphorylated AMPK following a decrease in all phosphorylatedforms of AKT, mTOR and S6K after the treatmentwith celastrol. Moreover, gastric tumor burdens were reducedin a dose-dependent manner by celastrol administration in axenografted mice model. Taken together, celastrol distinctlyinhibits the gastric cancer cell proliferation and induces autophagyand apoptosis.
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