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

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 c...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e79d9a1528004582b599d5a67e27bffe
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spelling	oai:doaj.org-article:e79d9a1528004582b599d5a67e27bffe2021-12-02T15:53:45ZElevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer10.1038/s41598-021-84852-z2045-2322https://doaj.org/article/e79d9a1528004582b599d5a67e27bffe2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84852-zhttps://doaj.org/toc/2045-2322Abstract 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.Tulin DadaliAnne R. DiersShiva KazerounianSenthil K. MuthuswamyPallavi AwateRyan NgSaie MogreCarrie SpencerKaterina KrumovaHannah E. RockwellJustice McDanielEmily Y. ChenFei GaoKarl T. DiedrichVijetha VemulapalliLeonardo O. RodriguesViatcheslav R. AkmaevKhampaseuth ThapaManuel HidalgoArindam BoseVivek K. VishnudasA. James MoserElder GrangerMichael A. KiebishStephane GestaNiven R. NarainRangaprasad SarangarajanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
description	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.
format	article
author	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
author_facet	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
author_sort	Tulin Dadali
title	Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer
title_short	Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer
title_full	Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer
title_fullStr	Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer
title_full_unstemmed	Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer
title_sort	elevated levels of mitochondrial coq10 induce ros-mediated apoptosis in pancreatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e79d9a1528004582b599d5a67e27bffe
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Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer

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