Coenzyme Q10 exerts anti-cancer effects in bladder cancer by inducing ROS-mediated apoptosis and autophagy.

Abstract

Bladder cancer (BCa) is one of the most common types of cancer that impacts the urinary system, and its incidence is increasing worldwide. Coenzyme Q10 (CoQ10) is a naturally occurring fat-soluble quinone with anti-oxidant and anti-inflammatory properties, and it plays a significant role in the suppression of tumor growth. Our objective was to elucidate the potential molecular mechanisms by which CoQ10 affects the advancement of BCa. In our study, human BCa cells 5637 and T24 and normal ureteral epithelial cells SV-Huc-1 were treated with different concentrations of CoQ10. Cell viability, reactive oxygen species (ROS) levels, apoptosis rate, and autophagy levels were assessed by CCK-8 assay, ROS assay kits, flow cytometry, reverse transcription quantitative PCR (RT-qPCR), and western blot analysis. Additionally, xenograft mouse models were conducted to investigate tumor growth. Our data indicated that CoQ10 decreased the viability of 5637 and T24 cells in a concentration- and time-dependent manner, while having minimal impact on SV-Huc-1 cells. Functional experiments uncovered that CoQ10 suppressed cell proliferation, and increased ROS levels, apoptosis, and autophagy in BCa cells. The application of the ROS inhibitor N-Acetyl-L-cysteine (NAC) significantly mitigated these effects. Furthermore, CoQ10 was found to block the Keap1-Nrf2 pathway, whereas the activator of Nrf2 (tert-Butylhydroquinone, TBHQ) and the agonist of HO-1 (Hemin) partially reversed CoQ10-induced ROS accumulation, apoptosis, and autophagy. In the BCa mouse model, CoQ10 inhibited tumor growth, apoptosis, autophagy, and the Keap1-Nrf2 pathway. These findings demonstrated that CoQ10 could be a therapeutic agent for BCa by promoting ROS-mediated apoptosis and autophagy via the Keap1-Nrf2 pathway.