Elevated levels of mitochondrial CoQ 10 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 Q is a critical cof...
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| Veröffentlicht in: | Scientific reports 2021-03, Vol.11 (1), p.5749 |
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| creator | 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 |
| description | 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 Q
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 Q
(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. |
| doi_str_mv | 10.1038/s41598-021-84852-z |
| format | Article |
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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 Q
(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.</description><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-84852-z</identifier><identifier>PMID: 33707480</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Respiration ; Cell Survival ; Electron Transport Complex II - metabolism ; Glycerol-3-Phosphate Dehydrogenase (NAD+) ; Humans ; Membrane Potential, Mitochondrial ; Mice ; Mice, Nude ; Mitochondria - metabolism ; Organoids - pathology ; Oxidative Stress ; Oxygen Consumption ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Reactive Oxygen Species - metabolism ; Substrate Specificity ; Ubiquinone - analogs & derivatives ; Ubiquinone - metabolism</subject><ispartof>Scientific reports, 2021-03, Vol.11 (1), p.5749</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,862,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33707480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dadali, Tulin</creatorcontrib><creatorcontrib>Diers, Anne R</creatorcontrib><creatorcontrib>Kazerounian, Shiva</creatorcontrib><creatorcontrib>Muthuswamy, Senthil K</creatorcontrib><creatorcontrib>Awate, Pallavi</creatorcontrib><creatorcontrib>Ng, Ryan</creatorcontrib><creatorcontrib>Mogre, Saie</creatorcontrib><creatorcontrib>Spencer, Carrie</creatorcontrib><creatorcontrib>Krumova, Katerina</creatorcontrib><creatorcontrib>Rockwell, Hannah E</creatorcontrib><creatorcontrib>McDaniel, Justice</creatorcontrib><creatorcontrib>Chen, Emily Y</creatorcontrib><creatorcontrib>Gao, Fei</creatorcontrib><creatorcontrib>Diedrich, Karl T</creatorcontrib><creatorcontrib>Vemulapalli, Vijetha</creatorcontrib><creatorcontrib>Rodrigues, Leonardo O</creatorcontrib><creatorcontrib>Akmaev, Viatcheslav R</creatorcontrib><creatorcontrib>Thapa, Khampaseuth</creatorcontrib><creatorcontrib>Hidalgo, Manuel</creatorcontrib><creatorcontrib>Bose, Arindam</creatorcontrib><creatorcontrib>Vishnudas, Vivek K</creatorcontrib><creatorcontrib>Moser, A James</creatorcontrib><creatorcontrib>Granger, Elder</creatorcontrib><creatorcontrib>Kiebish, Michael A</creatorcontrib><creatorcontrib>Gesta, Stephane</creatorcontrib><creatorcontrib>Narain, Niven R</creatorcontrib><creatorcontrib>Sarangarajan, Rangaprasad</creatorcontrib><title>Elevated levels of mitochondrial CoQ 10 induce ROS-mediated apoptosis in pancreatic cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>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 Q
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(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.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Respiration</subject><subject>Cell Survival</subject><subject>Electron Transport Complex II - metabolism</subject><subject>Glycerol-3-Phosphate Dehydrogenase (NAD+)</subject><subject>Humans</subject><subject>Membrane Potential, Mitochondrial</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mitochondria - metabolism</subject><subject>Organoids - pathology</subject><subject>Oxidative Stress</subject><subject>Oxygen Consumption</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Substrate Specificity</subject><subject>Ubiquinone - analogs & derivatives</subject><subject>Ubiquinone - metabolism</subject><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFTksKwjAUDIKoqBdwIe8C0fyK6VoUd-Jn5abENGKkbUJSBT29QXTtbGZgPgxCE0pmlHA5j4JmucSEUSyFzBh-ddCAEZFhxhnro3GMN5KQsVzQvIf6nC_IQkgyQKdVZR6qNSUkNlUEd4Hatk5fXVMGqypYuh1QArYp79rAfnvAtSntp6K8862LNiYXvGp0MKq1GnSSJoxQ96KqaMZfHqLpenVcbrC_n9NE4YOtVXgWvzP8b-ANpZtFsA</recordid><startdate>20210311</startdate><enddate>20210311</enddate><creator>Dadali, Tulin</creator><creator>Diers, Anne R</creator><creator>Kazerounian, Shiva</creator><creator>Muthuswamy, Senthil K</creator><creator>Awate, Pallavi</creator><creator>Ng, Ryan</creator><creator>Mogre, Saie</creator><creator>Spencer, Carrie</creator><creator>Krumova, Katerina</creator><creator>Rockwell, Hannah E</creator><creator>McDaniel, Justice</creator><creator>Chen, Emily Y</creator><creator>Gao, Fei</creator><creator>Diedrich, Karl T</creator><creator>Vemulapalli, Vijetha</creator><creator>Rodrigues, Leonardo O</creator><creator>Akmaev, Viatcheslav R</creator><creator>Thapa, Khampaseuth</creator><creator>Hidalgo, Manuel</creator><creator>Bose, Arindam</creator><creator>Vishnudas, Vivek K</creator><creator>Moser, A James</creator><creator>Granger, Elder</creator><creator>Kiebish, Michael A</creator><creator>Gesta, Stephane</creator><creator>Narain, Niven R</creator><creator>Sarangarajan, Rangaprasad</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20210311</creationdate><title>Elevated levels of mitochondrial CoQ 10 induce ROS-mediated apoptosis in pancreatic cancer</title><author>Dadali, Tulin ; 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Chemotherapy and radiation can induce ROS to elicit cell death allows for targeting ROS pathways for effective anti-cancer therapeutics. Coenzyme Q
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 Q
(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.</abstract><cop>England</cop><pmid>33707480</pmid><doi>10.1038/s41598-021-84852-z</doi></addata></record> |
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| subjects | Animals Apoptosis Cell Line, Tumor Cell Proliferation Cell Respiration Cell Survival Electron Transport Complex II - metabolism Glycerol-3-Phosphate Dehydrogenase (NAD+) Humans Membrane Potential, Mitochondrial Mice Mice, Nude Mitochondria - metabolism Organoids - pathology Oxidative Stress Oxygen Consumption Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Reactive Oxygen Species - metabolism Substrate Specificity Ubiquinone - analogs & derivatives Ubiquinone - metabolism |
| title | Elevated levels of mitochondrial CoQ 10 induce ROS-mediated apoptosis in pancreatic cancer |
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