Dihydroartemisinin Induces ER Stress-Mediated Apoptosis in Human Tongue \nSquamous Carcinoma by Regulating ROS Production

Background: Tongue squamous cell carcinoma is a fatal disease characterized by high invasion and early metastasis. Dihydroartemisinin, an antimalarial drug with multiple biological activities, is reported to be a potential anti-cancer agent. Objective: This study aimed to evaluate the antitumor effect of Dihydroartemisinin on tongue squamous cell carcinoma cells, and to identify the underlying mechanisms of Dihydroartemisinin-induced cell apoptosis. Methods: Here, Cell Counting Kit 8 assay and colony formation assay were conducted to study cell proliferation. Annexin V-FITC/propidium iodide staining and western blot analysis were performed to analyze cell apoptosis. DCFH-DA probe was used to measure the generation of cellular reactive oxygen species. Endoplasmic reticulum stress activation was also determined via western blot analysis. Results: The results showed that Dihydroartemisinin substantially inhibited cell proliferation and induced cell apoptosis in vivo. Moreover, reactive oxygen species production and endoplasmic reticulum stress activation were both observed after stimulation with Dihydroartemisinin. However, the reactive oxygen species inhibitor N-acetylcysteine significantly alleviated Dihydroartemisinin-induced endoplasmic reticulum stress and apoptosis. Conclusion: These results imply that Dihydroartemisinin induced cell apoptosis by triggering reactive oxygen species-mediated endoplasmic reticulum stress in CAL27 cells. In addition, Dihydroartemisinin might be an effective drug for tongue squamous cell carcinoma therapy.

Automated summary

This study found that Dihydroartemisinin can inhibit the proliferation of tongue squamous cell carcinoma cells and induce apoptosis, as well as stimulate the production of reactive oxygen species and activate endoplasmic reticulum stress. However, the use of a reactive oxygen species inhibitor can alleviate the endoplasmic reticulum stress and apoptosis induced by Dihydroartemisinin.