Coenzyme Q0, a quinone derivative from Antrodia camphorata, triggered ROS-mediated cytoprotective autophagy in human promyelocytic leukemia cells

From the paper

Abstract

Our previous investigation revealed that Coenzyme Q₀ (CoQ₀), a quinone derivative from Antrodia camphorata, triggered ROS-dependent voltage-dependent anion channel 1 (VDAC-1)-mediated apoptosis in human promyelocytic leukemia (HL-60) cells. This research examined the efficacies of CoQ₀ (0–7 μM) on autophagy induction and the interaction between apoptosis and autophagy in HL-60 cells. CoQ₀-triggered autophagy was associated with LC3-I/II accumulation, p62/SQSTM1 activation, autolysosome AVOs formation, ATG4B inhibition, ATG5/ATG7 expression, and Beclin-1/Bcl-2 dysregulation in HL-60 cells. Additionally, antioxidant N-acetylcysteine (NAC) prevented CoQ₀-induced autophagy in HL-60 cells. Surprisingly, CoQ₀-triggered cell death was enhanced by autophagy inhibitor 3-MA or CQ, indicating that autophagy acts as a survival mechanism. Additionally, autophagy suppression via 3-MA and/or CQ inhibitors strengthened the CoQ₀-induced ROS generation and apoptosis (caspase-3 activation). Apoptosis suppression by caspase inhibitor Z-VAD-FMK or VDAC-1 silencing prevented the CoQ₀-enhanced autophagy in HL-60 cells. Therefore, CoQ₀ together with autophagy inhibitors could be a potential therapy for human promyelocytic leukemia.