Curcumin derivative ST09 modulates the miR-199a-5p/DDR1 axis and regulates proliferation and migration in ovarian cancer cells

Abstract

Ovarian cancers are among the fatal malignancies affecting women globally, mainly due to their metastatic and chemoresistant nature. In this study, we report a potent curcumin derivative ST09 effective against ovarian cancers. Prior in-vitro studies with ST09 drug showed cytotoxicity in tumorigenic cells compared to normal cells and in-vivo, significant tumor reduction was observed with least systemic toxicity. ST09 induced cytotoxicity in the ovarian cancer cells triggering mitochondria-mediated intrinsic apoptotic pathway. Delving deeper to understand the underlying molecular mechanisms involved in ovarian cancer pathogenesis, we identified an inverse correlation of miR-199a-5p with DDR1, a collagen receptor with receptor tyrosine kinase activity. The ST09 treatment in ovarian cancer cell lines resulted in the deregulation of the miR-199a-5p/DDR1 axis, conferring tumor-suppressive functions. We established DDR1 to be a direct target of miR-199a-5p and that ST09-induced DDR1 loss in these ovarian cancer cells resulted in the inactivation of its downstream MMP activation, migration, EMT, and prosurvival NF-κB pathway. Overall this study demonstrates ST09, a potent drug candidate for ovarian cancer treatment which exhibits anti-invasive and migrastatic properties.