Isoalantolactone induces apoptosis through reactive oxygen species-dependent upregulation of death receptor 5 in human esophageal cancer cells.
Esophageal cancer is the eighth most prevalent cancer and has high mortality in our society. Isoalantolactone, extracted from Inula helenium L, has shown potent anticancer effects on a variety of cancers. However, its effect on human esophageal cancer, and the underlying molecular mechanism, remain to be investigated. In the present study, we demonstrated that isoalantolactone induced apoptosis in esophageal cancer cells. Treatment with isoalantolactone activated caspases-3, -7, and -10, and upregulated death receptor (DR)5. Furthermore, DR5 knockdown partially reversed the effect of isoalantolactone. These results indicated the extrinsic apoptosis was induced by isoalantolactone. In addition, intracellular reactive oxygen species (ROS) were significantly elevated after treatment with isoalantolactone. N-Acetylcysteine, an ROS scavenger, blocked both the apoptosis and decreased cell viability caused by isoalantolactone. In vivo, significant suppression of tumor growth by isoalantolactone was observed in an ECA109 cell xenograft mouse model. Isoalantolactone showed no obvious adverse effects on mouse weight and histology of heart, liver, spleen, lung, and kidney. In conclusion, our results revealed that isoalantolactone induced apoptosis through the extrinsic pathway via upregulation of DR5 and elevation of ROS in human esophageal cancer cells. Isoalantolactone, therefore, could be a potential candidate in developing anticancer agents for esophageal cancer patients.
['Lu|Zhengyang|Z|', 'Zhang|Guangxin|G|', 'Zhang|Yifan|Y|', 'Hua|Peiyan|P|', 'Fang|Meidan|M|', 'Wu|Meiliang|M|', 'Liu|Tongjun|T|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D004938:Esophageal Neoplasms D006801:Humans D008807:Mice, Inbred BALB C D008819:Mice, Nude D018384:Oxidative Stress D017382:Reactive Oxygen Species D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand D012717:Sesquiterpenes D015398:Signal Transduction D015854:Up-Regulation D023041:Xenograft Model Antitumor Assays
Isoalantolactone Apoptosis Death receptor 5 Esophageal cancer ROS