Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

AimsProstate cancer (PCa) is one of the most common cancers in men in the world. Advanced PCa, especially castration-resistant PCa (CRPC), is difficult to cure. There is an urgent need to develop novel agents for CPRC. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and is a well-known antimalarial drug. DHA has been documented to be a potential anticancer agent for PCa. However, the mechanisms underlying the anticancer activity of DHA are still unknown.Main methodsProteomics analysis based on iTRAQ technology was performed to determine the protein profile changes in human prostate cancer PC3 cells treated by DHA, and apoptosis was detected by flow cytometry and transmission electron microscopy.Key findingsDHA induced obvious apoptosis in PC3 cells. Using iTRAQ technology, we found 86 differentially expressed proteins linked to the cytotoxicity of DHA in PC3 cells. Gene ontology analysis showed the differentially expressed proteins were mainly associated with the protein synthesis and translation. Protein interaction network analysis and KEGG pathway analysis revealed altered aminoacyl-tRNA biosynthesis and metabolic pathways. Moreover, one candidate protein, heat shock protein HSP70 (HSPA1A), was identified by western blot analysis.SignificanceOur results indicate that multiple mechanisms involved in the anticancer activity of DHA in PC3 cells. Decreased HSP70 expression may have an important role in DHA-induced apoptosis in PC3 cells. Our data also provide novel insights into the anticancer mechanisms of DHA.