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

Antrodia camphorata (AC) and Coenzyme Q (CoQ ), a novel quinone derivative of AC, exhibits antitumor activities. The present study evaluated EMT/metastasis inhibition and autophagy induction aspects of AC and CoQ 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 (0-10 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 treatment. In addition, MMP-2/-9 expression and Wnt/β-catenin pathways were downregulated. Furthermore, autophagy inhibitors 3-MA or CQ reversed the CoQ -elicited suppression of migration/invasion and metastasis-related proteins (Vimentin, Snail, and β-catenin). Results suggested autophagy-mediated antiEMT and antimetastasis upon CoQ treatment. CoQ inhibited HIF-1α and metastasis in GBM8401 cells under normoxia and hypoxia. HIF-1α knockdown using siRNA accelerated CoQ -inhibited migration. Finally, CoQ exhibited a prolonged survival rate in GBM8401-xenografted mice. Treatment with Antrodia camphorata/CoQ inhibited HIF-1α and EMT/metastasis in glioblastoma.