Antrodia camphorata and coenzyme Q0, a novel quinone derivative of Antrodia camphorata, impede HIF‐1α and epithelial‐mesenchymal transition/metastasis in human glioblastoma cells

Abstract

AbstractAntrodia camphorata (AC) and Coenzyme Q0 (CoQ0), a novel quinone derivative of AC, exhibits antitumor activities. The present study evaluated EMT/metastasis inhibition and autophagy induction aspects of AC and CoQ0 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 CoQ0 (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 CoQ0 treatment. In addition, MMP‐2/‐9 expression and Wnt/β‐catenin pathways were downregulated. Furthermore, autophagy inhibitors 3‐MA or CQ reversed the CoQ0‐elicited suppression of migration/invasion and metastasis‐related proteins (Vimentin, Snail, and β‐catenin). Results suggested autophagy‐mediated antiEMT and antimetastasis upon CoQ0 treatment. CoQ0 inhibited HIF‐1α and metastasis in GBM8401 cells under normoxia and hypoxia. HIF‐1α knockdown using siRNA accelerated CoQ0‐inhibited migration. Finally, CoQ0 exhibited a prolonged survival rate in GBM8401‐xenografted mice. Treatment with Antrodia camphorata/CoQ0 inhibited HIF‐1α and EMT/metastasis in glioblastoma.