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

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.

SUBMITTER: Hseu YC

PROVIDER: S-EPMC5556069 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Hseu You-Cheng YC Tsai Tai-Jung TJ Korivi Mallikarjuna M Liu Jer-Yuh JY Chen Hui-Jye HJ Lin Chung-Ming CM Shen Yi-Chun YC Yang Hsin-Ling HL

Scientific reports 20170814 1

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</ ...[more]

PMID: 28808311

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Dataset Information

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

Publications

Antitumor properties of Coenzyme Q<sub>0</sub> against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy.

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