Antitumor properties of Coenzyme Q(0) against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy

作者：Hseu You Cheng; Tsai Tai Jung; Korivi Mallikarjuna; Liu Jer Yuh; Chen Hui Jye; Lin Chung Ming; Shen Yi Chun; Yang Hsin Ling

来源：Scientific Reports, 2017, 7(1): 8062.

DOI：10.1038/s41598-017-08659-7

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 PI3K/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.

• 出版日期2017-8-14
• 单位中国医科大学