Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer.

Reactive oxygen species (ROS) are implicated in triggering cell signalling events and pathways to promote and maintain tumorigenicity. Chemotherapy and radiation can induce ROS to elicit cell death allows for targeting ROS pathways for effective anti-cancer therapeutics. Coenzyme Q10 is a critical cofactor in the electron transport chain with complex biological functions that extend beyond mitochondrial respiration. This study demonstrates that delivery of oxidized Coenzyme Q10 (ubidecarenone) to increase mitochondrial Q-pool is associated with an increase in ROS generation, effectuating anti-cancer effects in a pancreatic cancer model. Consequent activation of cell death was observed in vitro in pancreatic cancer cells, and both human patient-derived organoids and tumour xenografts. The study is a first to demonstrate the effectiveness of oxidized ubidecarenone in targeting mitochondrial function resulting in an anti-cancer effect. Furthermore, these findings support the clinical development of proprietary formulation, BPM31510, for treatment of cancers with high ROS burden with potential sensitivity to ubidecarenone.

Citation

Tulin Dadali, Anne R Diers, Shiva Kazerounian, Senthil K Muthuswamy, Pallavi Awate, Ryan Ng, Saie Mogre, Carrie Spencer, Katerina Krumova, Hannah E Rockwell, Justice McDaniel, Emily Y Chen, Fei Gao, Karl T Diedrich, Vijetha Vemulapalli, Leonardo O Rodrigues, Viatcheslav R Akmaev, Khampaseuth Thapa, Manuel Hidalgo, Arindam Bose, Vivek K Vishnudas, A James Moser, Elder Granger, Michael A Kiebish, Stephane Gesta, Niven R Narain, Rangaprasad Sarangarajan. Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer. Scientific reports. 2021 Mar 11;11(1):5749

Mesh Tags

Substances

PMID: 33707480

search → result