| Abstrakt: |
Background: Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi. Aim: The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line. Methods: The MTT assay was used to unravel the antiproliferative effects of gaillardin on MCF-7 cells. The expression of apoptosis-related genes including CASP3, BAX, BCL2, STAT3, and JAK2, and key markers of autophagy such as ATG1, ATG4, ATG5, ATG7, ATG12, BECN1, and MAP1LC3A were measured by real time-PCR method. The protein expression of Caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III was determined using western blotting. Results: Gaillardin treatment significantly decreased the proliferation of MCF-7 cells with a parallel upregulation of the level of pro-apoptotic caspase-3 enzyme with no effect on Bax and Bcl2 expression. The levels of phosphorylated and active forms of JAK2 and STAT3 proteins were reduced following the treatment of MCF-7 cells with gaillardin. This sesquiterpene lactone com-pound considerably downregulated the levels of six autophagy markers, including ATG1, ATG4, ATG5, ATG12, Beclin1, and LC-III in MCF-7 cells. Conclusion: These data indicated the apoptosis-inducing activity of gaillardin in MCF-7 cells by a mechanism that inhibits the JAK/STAT signaling pathway. Further, autophagy inhibition was the other phenomenon caused by gaillardin in MCF-7 cells. These results can provide evidence to highlight the role of gaillardin as a novel therapeutic for the treatment of breast cancer. [ABSTRACT FROM AUTHOR] |
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