Gaillardin inhibits autophagy and induces apoptosis in MCF-7 breast cancer cells by regulating JAK/STAT pathway

• DOI: 10.1007/s11033-023-09131-8
• Publication Date: 2024-01-22T09:02:18Z
• Authors: Sadegh Rajabi; Zahra Tahmasvand; Marc Maresca; Maryam Hamzeloo-M...
• Keywords: Apoptosis; Gaillardin; STAT3; STAT Transcription Factors; Lactones; Breast cancer; JAK2; [SDV.CAN] Life Sciences [q-bio]/Cancer; Proto-Oncogene Proteins c-bcl-2; [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; Neoplasms; [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; MCF-7 Cells; Autophagy; Humans; Beclin-1; Sesquiterpenes; Janus Kinases; bcl-2-Associated X Protein; Signal Transduction

Gaillardin is a potent anti-cancer sesquiterpene lactone found in Inula oculus-christi.The present study examined the effects of gaillardin on apoptosis and autophagy in the MCF-7 breast cancer cell line.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.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.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.