In vitro and in vivo anti-tumor activity of Coenzyme Q<inf>0</inf> against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction
Issued Date
2023-04-15
Resource Type
ISSN
0041008X
eISSN
10960333
Scopus ID
2-s2.0-85150306318
Pubmed ID
36914119
Journal Title
Toxicology and Applied Pharmacology
Volume
465
Rights Holder(s)
SCOPUS
Bibliographic Citation
Toxicology and Applied Pharmacology Vol.465 (2023)
Suggested Citation
Yang H.L., Chiu L.W., Lin Y.A., Pandey S., Vadivalagan C., Liao J.W., Gowrisankar Y.V., Chen H.J., Lin H.Y., Hseu Y.C. In vitro and in vivo anti-tumor activity of Coenzyme Q<inf>0</inf> against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction. Toxicology and Applied Pharmacology Vol.465 (2023). doi:10.1016/j.taap.2023.116453 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82196
Title
In vitro and in vivo anti-tumor activity of Coenzyme Q<inf>0</inf> against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction
Author's Affiliation
Other Contributor(s)
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 Q0 (CoQ0, 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 CoQ0 effectively reduced cell viability and displayed rapid morphological changes in FaDu-TWIST1 cells compared to FaDu cells. Non/sub-cytotoxic concentrations of CoQ0 treatment reduces the cell migration by downregulating TWIST1 and upregulating E-cadherin. Apoptosis produced by CoQ0 was mostly related with caspase-3 activation, PARP cleavage, and VDAC-1 expression. The FaDu-TWIST1 cells treated with CoQ0 exhibits autophagy-mediated LC3-II accumulation and acidic vesicular organelles (AVOs) formation. Pre-treatment with 3-MA and CoQ effectively prevented CoQ0-induced cell death and CoQ0-triggered autophagy in FaDu-TWIST cells as a death mechanism. CoQ0 induces ROS production in FaDu-TWIST1 cells and NAC pre-treatment significantly reduces anti-metastasis, apoptosis, and autophagy. Likewise, ROS-mediated AKT inhibition regulates CoQ0-induced apoptosis/autophagy in FaDu-TWIST1 cells. In vivo studies exhibit, CoQ0 effectively delays and reduces the tumor incidence and burden in FaDu-TWIST1-xenografted nude mice. Current findings display, CoQ0 exhibits a novel anti-cancer mechanism hence, it might be appropriate for anticancer therapy, and a new potent drug for HNSCC.