Harnessing the power of gaillardin: A natural sesquiterpene with anti-ovarian Cancer potential

Abstract

Ovarian cancer is the eighth most frequent cancer and fifth most common cause of death in women in the world. Gaillardin is a sesquiterpene lactone with an anti-tumor effect on different cancers. This study explored the anti-proliferative and pro-apoptotic effect of gaillardin on the ovarian cancer cell line SKOV3. The proliferation level of SKOV3 cells was assayed using the MTT method. Then, IC₅₀ values for the gaillardin treatment of SKOV3 cells were calculated. The apoptotic death-inducing feature of SKOV3 cells following gaillardin treatment was assessed by flow cytometry. The time-PCR method was used to measure the gene transcript amount of apoptosis markers CASP3, CASP8, CASP9, BAX, BCL2, STAT3, and JAK2. The protein levels of the markers mentioned above were semiquantified using western blotting. Gaillardin significantly inhibited the proliferation of SKOV3 cells compared with the controls. Moreover, the gaillardin-treated SKOV3 cells underwent apoptotic cell death in comparison to the untreated cell line. The results of real-time PCR analysis unraveled that gaillardin treatment significantly upregulated the expression of CASP3, CASP8, CASP9, and BAX but downregulated BCL-2 with no influence on the expression levels of STAT3 and JAK2 transcripts. This sesquiterpene had identical effects on the protein expression of caspases, Bax, and Bcl2. However, it downregulated the phosphorylated forms of JAK2 and STAT3 proteins. Our data indicated that gaillardin may act as an anticancer drug to inhibit the proliferation and induce apoptosis in ovarian cancer cells by triggering the intrinsic and extrinsic pathways of apoptosis and the blockage of the JAK/STAT signaling pathway.