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.

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Citation abstract

Coenzyme Q 0 (CoQ 0, 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 CoQ 0 on human glioblastoma both in vitro and in vivo, and explained the molecular mechanism behind it. CoQ 0 treatment retarded the growth and suppressed colony formation in glioblastoma (U87MG and GBM8401) cells. CoQ 0 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 CoQ 0 mediated necrosis and apoptosis. Interestingly, AVOs were increased trough induction of autophagy by CoQ 0, LC3-II accumulation, and p62/SQSTM1 expression, leading to death mechanism. Z-VAD-FMK has no effect on CoQ 0 -induced autophagy but autophagy inhibition by 3-methyladenine (3-MA)/chloroquine (CQ) led to CoQ 0 -induced apoptosis. N-acetylcysteine (NAC) inhibited CoQ 0 -mediated ROS production and diminished CoQ 0 -induced apoptotic and autophagic cell death. Further, CoQ 0 inhibited PI3K/AKT/mTOR signaling pathways. CoQ 0 reduced the tumor burden in U87MG and GBM8401 xenografted athymic nude mice and significantly modulated tumor xenograft by inducing apoptosis and autophagy. CoQ 0 generated ROS-mediated apoptotic and autophagic cell death for effective glioblastoma treatment.