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

Author:

Dadali Tulin,Diers Anne R.,Kazerounian Shiva,Muthuswamy Senthil K.,Awate Pallavi,Ng Ryan,Mogre Saie,Spencer Carrie,Krumova Katerina,Rockwell Hannah E.,McDaniel Justice,Chen Emily Y.,Gao Fei,Diedrich Karl T.,Vemulapalli Vijetha,Rodrigues Leonardo O.,Akmaev Viatcheslav R.,Thapa Khampaseuth,Hidalgo Manuel,Bose Arindam,Vishnudas Vivek K.,Moser A. James,Granger Elder,Kiebish Michael A.,Gesta Stephane,Narain Niven R.,Sarangarajan Rangaprasad

Abstract

AbstractReactive 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.

Funder

BERG LLC

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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