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

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