2. Academic Validation
  3. Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy

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

  • Sci Rep. 2017 Aug 14;7(1):8062. doi: 10.1038/s41598-017-08659-7.
You-Cheng Hseu 1 2,  Tai-Jung Tsai 3,  Mallikarjuna Korivi 3,  Jer-Yuh Liu 4,  Hui-Jye Chen 5,  Chung-Ming Lin 6,  Yi-Chun Shen 3,  Hsin-Ling Yang 7
Affiliations

Affiliations

  • 1 Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan.
  • 2 Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan.
  • 3 Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan.
  • 4 Graduate Institute of Cancer Biology, China Medical University, Taichung, 40402, Taiwan.
  • 5 Graduate Institute of Basic Medical Science, China Medical University, Taichung, 402, Taiwan.
  • 6 Department of Biotechnology, Ming Chuan University, Taoyuan, 333, Taiwan.
  • 7 Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, 40402, Taiwan. [email protected].
PMID: 28808311 DOI: 10.1038/s41598-017-08659-7
Abstract

Coenzyme Q0 (CoQ0, 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 CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-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 CoQ0-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, CoQ0-induced Apoptosis/Autophagy is associated with suppression of HER-2/neu and PI3K/Akt signalling cascades. CoQ0 triggered intracellular ROS production, whereas antioxidant N-acetylcysteine prevented CoQ0-induced Apoptosis, but not Autophagy. Inhibition of Apoptosis by Z-VAD-FMK suppressed CoQ0-induced Autophagy (diminished LC3-II/AVOs), indicates CoQ0-induced Apoptosis led to evoke Autophagy. Contrary, inhibition of Autophagy by 3-MA/CQ potentiated CoQ0-induced Apoptosis (increased DNA fragmentation/PARP cleavage). Furthermore, CoQ0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden. Histopathological analyses confirmed that CoQ0 modulated xenografted tumor progression by Apoptosis induction. Our findings emphasize that CoQ0 triggered ROS-mediated Apoptosis and cytoprotective Autophagy.

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