Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy

Abstract

Abstract Coenzyme Q 0 (CoQ 0 , 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ 0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ 0 induced G 2 /M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ 0 -induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation. Increased TUNEL-positive cells and Annexin-V/PI stained cells indicated CoQ 0 -induced late apoptosis. Both mitochondrial (caspase-3, PARP and Bax/Bcl-2 dysregulation) and ER stress (caspase-12 and Hsp70) signals are involved in execution of apoptosis. Interestingly, CoQ 0 -induced apoptosis/autophagy is associated with suppression of HER-2/ neu and PI 3 K/AKT signalling cascades. CoQ 0 triggered intracellular ROS production, whereas antioxidant N -acetylcysteine prevented CoQ 0 -induced apoptosis, but not autophagy. Inhibition of apoptosis by Z-VAD-FMK suppressed CoQ 0 -induced autophagy (diminished LC3-II/AVOs), indicates CoQ 0 -induced apoptosis led to evoke autophagy. Contrary, inhibition of autophagy by 3-MA/CQ potentiated CoQ 0 -induced apoptosis (increased DNA fragmentation/PARP cleavage). Furthermore, CoQ 0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden. Histopathological analyses confirmed that CoQ 0 modulated xenografted tumor progression by apoptosis induction. Our findings emphasize that CoQ 0 triggered ROS-mediated apoptosis and cytoprotective autophagy.