Cinnamaldehyde enhances cytotoxic effect of cisplatin by ROS-induced autophagy in cisplatin-resistant ovarian cancer cells.

Abstract

Ovarian cancer is the most lethal gynecologic cancer. A major obstacle to the current therapy for ovarian cancer is the platinum-resistance. Cisplatin (CDDP) is representatively platinum-based drug and has anti-cancer effect by triggering reactive oxygen species (ROS) in various cancer cells. Cinnamaldehyde (CA), extracted from the stem bark of Cinnamomum cassia, has been shown to possess anticancer effects in various cancers and to induce apoptotic cell death by ROS generation. According to previous studies, induction of ROS by cellular stressors promotes autophagic cell death as well as apoptosis in many cancers. So, we tested whether CA and CDDP boost ROS-mediated apoptosis and autophagy and also have synergistic effect in ovarian cancer cells. We chose two types of ovarian cancer cell lines (A2780/s sensitive to CDDP and A2780/cis resistant to CDDP). Low dose (1 µM) of CDDP appeared cytotoxicity and induced ROS-mediated apoptosis and autophagy in A2780/s. But high dose (10 µM) of CDDP was not affected in A2780/cis. In this condition, co-treatment of CA remarkably increased synergistic growth-inhibitory effect and induced ROS-mediated apoptosis and autophagy in A2780/cis. Thus, excessive ROS by combination of CA and CDDP might be proposed to a way to overcome the chemoresistance in ovarian cancer.