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.

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells

“…It has found that amino acid metabolism and glycerphospholipid metabolism were the most important metabolic pathways [5]. We have demonstrated that parthenolide leaded to proteomic differences in BCPAP cells before [13].…”

“…These results indicated that parthenolide could inhibit the development and proliferation of PTC cells by accelerating oxidative stress response and metabolic imbalance, especially in amino acid and lipid changes [5,12]. Then we demonstrated that parthenolide could lead to proteomic differences in PTC cells (BCPAP cells) [13].…”

“…Su cient cell samples were divided into 12 groups. According to the appropriate concentration (IC50) explored in the preliminary experiment [13], parthenolide was dissolved in 0.05% DMSO and diluted with PBS to 10 µmol/L and was added to each treatment group (n = 6) for 24 hours, and 6 control groups were added with the same amount of complete culture medium.…”

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells

“…Sufficient cell samples were divided into 12 groups. According to the appropriate concentration (IC50) explored in the preliminary experiment [ 13 ], parthenolide was dissolved in 0.05% DMSO and diluted with PBS to 10 μM and was added to each treatment group ( n = 6) for 24 h, and 6 control groups were added with the same amount of complete culture medium.…”

“…These findings indicate that parthenolide can inhibit the growth and proliferation of PTC cells by enhancing oxidative stress response and metabolic imbalance, particularly in terms of amino acid and lipid changes [ 5 , 12 ]. Furthermore, we demonstrated that parthenolide can lead to proteomic differences in PTC cells (BCPAP cells) [ 13 ].…”