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Abstract

Esophageal cancer (EC) is one of the most fatal malignancies worldwide. Dehydrocostus lactone (DHL) derived from the dried roots of Saussurea costus (Falc.) Lipech is a sesquiterpene lactone compound that exerts anticancer activities. In this study, DHL was obtained to evaluate its anti-esophageal cancer ability and underlying mechanism in vitro and in vivo . DHL inhibited the proliferation and migration of Eca109 and KYSE150 esophageal cancer cells in a time- and dose-dependent manner. Moreover, it inhibited the growth of Eca109 tumor xenografts in a dose-dependent manner with no significant signs of toxicity in the organs of nude mice . Mechanistically, treatment with DHL could significantly activate reactive oxygen species (ROS) in cells, leading to mitochondrial damage, and inducing apoptosis and autophagy. The ROS inhibitor N-acetyl-L-cysteine (NAC) inhibited DHL-induced apoptosis and autophagy. The pancaspase inhibitor Z-VAD-FMK diminished DHL-induced autophagy, but the autophagy inhibitor 3-methyladenine (3-MA) had no effect on DHL-induced apoptosis. Western blot analysis results indicated that the PI3K/Akt/Bad pathway participated in this process. In conclusion, DHL inhibits the proliferation of esophageal cancer cells through ROS-mediated apoptosis and autophagy in vivo and in vitro . All results suggest that DHL can be considered a potential chemotherapeutic drug for esophageal cancer.