In vitro and in vivo anti-tumor activity of Coenzyme Q0 against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction.

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Citation abstract

HNSCC (Head and Heck Squamous Cell Carcinoma) is a reasonably prevalent cancer with a high mortality rate. In this study, we tried to examine the anti-metastasis and apoptosis/autophagy actions of Coenzyme Q 0 (CoQ 0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a derivative of Antrodia camphorata in HNCC TWIST1 overexpressing (FaDu-TWIST1) cells as well as in vivo tumor xenograft mice model. Using fluorescence based cellular assays, western blot and nude mice tumor xenografts, we determined that CoQ 0 effectively reduced cell viability and displayed rapid morphological changes in FaDu-TWIST1 cells compared to FaDu cells. Non/sub-cytotoxic concentrations of CoQ 0 treatment reduces the cell migration by downregulating TWIST1 and upregulating E-cadherin. Apoptosis produced by CoQ 0 was mostly related with caspase-3 activation, PARP cleavage, and VDAC-1 expression. The FaDu-TWIST1 cells treated with CoQ 0 exhibits autophagy-mediated LC3-II accumulation and acidic vesicular organelles (AVOs) formation. Pre-treatment with 3-MA and CoQ effectively prevented CoQ 0 -induced cell death and CoQ 0 -triggered autophagy in FaDu-TWIST cells as a death mechanism. CoQ 0 induces ROS production in FaDu-TWIST1 cells and NAC pre-treatment significantly reduces anti-metastasis, apoptosis, and autophagy. Likewise, ROS-mediated AKT inhibition regulates CoQ 0 -induced apoptosis/autophagy in FaDu-TWIST1 cells. In vivo studies exhibit, CoQ 0 effectively delays and reduces the tumor incidence and burden in FaDu-TWIST1-xenografted nude mice. Current findings display, CoQ 0 exhibits a novel anti-cancer mechanism hence, it might be appropriate for anticancer therapy, and a new potent drug for HNSCC.