In vitro and in vivo anti-tumor activity of Coenzyme Q 0 against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction.

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 (CoQ, 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 effectively reduced cell viability and displayed rapid morphological changes in FaDu-TWIST1 cells compared to FaDu cells. Non/sub-cytotoxic concentrations of CoQ treatment reduces the cell migration by downregulating TWIST1 and upregulating E-cadherin. Apoptosis produced by CoQ was mostly related with caspase-3 activation, PARP cleavage, and VDAC-1 expression. The FaDu-TWIST1 cells treated with CoQ exhibits autophagy-mediated LC3-II accumulation and acidic vesicular organelles (AVOs) formation. Pre-treatment with 3-MA and CoQ effectively prevented CoQ-induced cell death and CoQ-triggered autophagy in FaDu-TWIST cells as a death mechanism. CoQ 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-induced apoptosis/autophagy in FaDu-TWIST1 cells. In vivo studies exhibit, CoQ effectively delays and reduces the tumor incidence and burden in FaDu-TWIST1-xenografted nude mice. Current findings display, CoQ exhibits a novel anti-cancer mechanism hence, it might be appropriate for anticancer therapy, and a new potent drug for HNSCC.