Coenzyme Q0, a novel quinone derivative of Antrodia camphorata, induces ROS-mediated cytotoxic autophagy and apoptosis against human glioblastoma cells in vitro and in vivo

• Published in: Food and chemical toxicology 2021-09, Vol.155, p.112384, Article 112384
• Main Authors: Yang, Hsin-Ling, Tsai, Chia-Hsuan, Shrestha, Sirjana, Lee, Chuan-Chen, Liao, Jiunn-Wang, Hseu, You-Cheng
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Coenzyme Q0; Glioblastoma; ROS
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112384

Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) derived from Antrodia camphorata exerts anticancer activities against breast, melanoma, and ovarian carcinoma. Glioblastoma multiforme is a common tumor affecting the central nervous system. This study explored anticancer properties of CoQ0 on human glioblastoma both in vitro and in vivo, and explained the molecular mechanism behind it. CoQ0 treatment retarded the growth and suppressed colony formation in glioblastoma (U87MG and GBM8401) cells. CoQ0 induced apoptosis by activation of caspase-3, cleavage of PARP, and dysregulation of Bax and Bcl-2 in both cell lines. Annexin V/PI staining indicated CoQ0 mediated necrosis and apoptosis. Interestingly, AVOs were increased trough induction of autophagy by CoQ0, LC3-II accumulation, and p62/SQSTM1 expression, leading to death mechanism. Z-VAD-FMK has no effect on CoQ0-induced autophagy but autophagy inhibition by 3-methyladenine (3-MA)/chloroquine (CQ) led to CoQ0-induced apoptosis. N-acetylcysteine (NAC) inhibited CoQ0-mediated ROS production and diminished CoQ0-induced apoptotic and autophagic cell death. Further, CoQ0 inhibited PI3K/AKT/mTOR signaling pathways. CoQ0 reduced the tumor burden in U87MG and GBM8401 xenografted athymic nude mice and significantly modulated tumor xenograft by inducing apoptosis and autophagy. CoQ0 generated ROS-mediated apoptotic and autophagic cell death for effective glioblastoma treatment. [Display omitted] •CoQ0, a quinone derived from Antrodia camphorata, reveals anti-glioblastoma activity.•CoQ0-induced apoptosis is accompanied by caspase-3 activation and PARP cleavage.•CoQ0 induced autophagic cell death associated with AVO and LC3-II formation.•Antioxidant NAC prevents CoQ0-induced ROS-mediated apoptosis and autophagy.•CoQ0 induces apoptosis and autophagy in U87MG and GBM8401 xenografted nude mice.