Parthenolide inhibited the growth and migration of MDA-T32 human papillary thyroid carcinoma cells.

PMID: 

Med Sci Monit. 2019 Jul 8 ;25:5054-5061. Epub 2019 Jul 8. PMID: 31322140

Abstract Title: 

Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

Abstract: 

BACKGROUNDThis study aimed to examine the effects of the sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of MDA-T32 human papillary thyroid carcinoma cellsin vitroand in mouse tumor xenografts.MATERIAL AND METHODSCell proliferation and viability of MDA-T32 human papillary thyroid carcinoma cells were determined by MTT assay, and cell migration was studied using a transwell assay. Fluorescence microscopy using acridine orange (AO) and ethidium bromide (EB) staining evaluated apoptosis. Transmission electron microscopy was used to study the effects of parthenolide on autophagy, and Western blot examined the levels of autophagy-associated proteins, including Bax, Bcl-2, and LC3-ll. Mice (n=10) were injected with 5×10⁶ MDA-T32 cells subcutaneously into the left flank, and xenograft tumors were grown for six weeks. Control untreated mice (n=5) were compared with treated mice (n=5) given parthenolide three times per week.RESULTSParthenolide resulted in a dose-dependent reduction in viability and cell migration of MDA-T32 cells, with a half-maximal inhibitory concentration (IC₅₀) of 12 µM. AO and EB staining showed that parthenolide induced cell apoptosis and electron microscopy identified autophagosomes in MDA-T32 cells. Parthenolide induced increased expression of the autophagocytic proteins, LC3-II and beclin-1, had a dose-dependent inhibitory effect on the mTOR/PI3K/AKT cascade in MDA-T32 cells and inhibited the growth of the mouse xenograft tumorsin vivo.CONCLUSIONSParthenolide inhibited the growth and migration of MDA-T32 human papillary thyroid carcinoma cellsin vitroand mouse tumor xenografts and activated autophagy and apoptosis by downregulation of the mTOR/PI3K/AKT signaling pathway.

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