Antrodia camphorata and coenzyme Q 0 , a novel quinone derivative of Antrodia camphorata , impede HIF ‐1α and epithelial‐mesenchymal transition/metastasis in human glioblastoma cells

Abstract Antrodia camphorata (AC) and Coenzyme Q 0 (CoQ 0 ), a novel quinone derivative of AC, exhibits antitumor activities. The present study evaluated EMT/metastasis inhibition and autophagy induction aspects of AC and CoQ 0 in human glioblastoma (GBM8401) cells. Our findings revealed that AC treatment (0–150 μg/mL) hindered tumor cell proliferation and migration/invasion in GBM8401 cells. Notably, AC treatment inhibited HIF‐1α and EMT by upregulating epithelial marker protein E‐cadherin while downregulating mesenchymal proteins Twist, Slug, Snail, and β‐catenin. There was an appearance of the autophagy markers LC3‐II and p62/SQSTM1, while ATG4B was downregulated by AC treatment. We also found that CoQ 0 (0–10 μM) could inhibit migration and invasion in GBM8401 cells. In particular, E‐cadherin was elevated and N‐cadherin, Vimentin, Twist, Slug, and Snail, were reduced upon CoQ 0 treatment. In addition, MMP‐2/‐9 expression and Wnt/β‐catenin pathways were downregulated. Furthermore, autophagy inhibitors 3‐MA or CQ reversed the CoQ 0 ‐elicited suppression of migration/invasion and metastasis‐related proteins (Vimentin, Snail, and β‐catenin). Results suggested autophagy‐mediated antiEMT and antimetastasis upon CoQ 0 treatment. CoQ 0 inhibited HIF‐1α and metastasis in GBM8401 cells under normoxia and hypoxia. HIF‐1α knockdown using siRNA accelerated CoQ 0 ‐inhibited migration. Finally, CoQ 0 exhibited a prolonged survival rate in GBM8401‐xenografted mice. Treatment with Antrodia camphorata /CoQ 0 inhibited HIF‐1α and EMT/metastasis in glioblastoma.