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

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

Authors :
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
Source :
Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
Publication Year :
2021
Publisher :
Nature Portfolio, 2021.

Abstract

Abstract 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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
20452322
Volume :
11
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.79d9a1528004582b599d5a67e27bffe
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-021-84852-z