Parthenolide leads to proteomic differences in thyroid cancer cells and promotes apoptosis

Abstract

Background: Parthenolide has anti-inflammatory, immunomodulatory and anti-cancer activities. But its effect on thyroid cancer cells is still largely unknown. Methods: Label-free quantitative proteomics and bioinformatics analysis were used to investigate the differentially expressed proteins and their functions in thyroid cancer treated with parthenolide and control pair. Hoechst 33258 fluorescent staining and Annexin V-FITC/PI double staining flow cytometry were used to detected BCPAP cells apoptosis. Parallel reaction monitoring (PRM) and quantitative real-time PCR were used to verify the expression of apoptosis-related differential proteins and their mRNA. Results: Sixty up-regulated and 96 down-regulated differentially expressed proteins were identified in parthenolide treated thyroid cancer cells BCPAP compared with control thyroid cancer cells. The proteins were mainly relevant to various biological processes that included metabolic processes, response to extracellular stimulus and interaction with host. The molecular functions of most differentially expressed proteins were associated with binding functions and nucleotidyltransferase activity. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways and DNA replication. In cell experiments in vitro, with the increase of the dose of parthenolide, the number of cells gradually decreased, the apoptosis rate gradually increased. PRM verified that the apoptosis-related proteins HMOX1 and GCLM were up-regulated and IL1B was down-regulated in BCPAP cells treated with parthenolide. The mRNA expressions of HMOX1, GCLM, ITGA6 and CASP8 were up-regulated and HSPA1A was down-regulated by PCR. Conclusions: Parthenolide may influence the biological behavior of human thyroid cancer cells by affecting the expression of proteins related to cell metabolism and DNA replication. Parthenolide induced significant cellular morphological changes and apoptosis in human thyroid cancer cells, leading to an anti-proliferative effect.