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Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent
Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067146/ https://www.ncbi.nlm.nih.gov/pubmed/35278276 http://dx.doi.org/10.1002/1878-0261.13209 |
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author | Jung, Minsun Lee, Kyung‐Min Im, Yebin Seok, Seung Hyeok Chung, Hyewon Kim, Da Young Han, Dohyun Lee, Cheng Hyun Hwang, Eun Hye Park, Soo Young Koh, Jiwon Kim, Bohyun Nikas, Ilias P. Lee, Hyebin Hwang, Daehee Ryu, Han Suk |
author_facet | Jung, Minsun Lee, Kyung‐Min Im, Yebin Seok, Seung Hyeok Chung, Hyewon Kim, Da Young Han, Dohyun Lee, Cheng Hyun Hwang, Eun Hye Park, Soo Young Koh, Jiwon Kim, Bohyun Nikas, Ilias P. Lee, Hyebin Hwang, Daehee Ryu, Han Suk |
author_sort | Jung, Minsun |
collection | PubMed |
description | Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM‐induced metabolic regulation and the therapeutic efficacy of NAM in triple‐negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β‐oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next‐generation anti‐metabolic agent for TNBC treatment. |
format | Online Article Text |
id | pubmed-9067146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90671462022-05-09 Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent Jung, Minsun Lee, Kyung‐Min Im, Yebin Seok, Seung Hyeok Chung, Hyewon Kim, Da Young Han, Dohyun Lee, Cheng Hyun Hwang, Eun Hye Park, Soo Young Koh, Jiwon Kim, Bohyun Nikas, Ilias P. Lee, Hyebin Hwang, Daehee Ryu, Han Suk Mol Oncol Research Articles Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM‐induced metabolic regulation and the therapeutic efficacy of NAM in triple‐negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β‐oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next‐generation anti‐metabolic agent for TNBC treatment. John Wiley and Sons Inc. 2022-03-25 2022-05 /pmc/articles/PMC9067146/ /pubmed/35278276 http://dx.doi.org/10.1002/1878-0261.13209 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Jung, Minsun Lee, Kyung‐Min Im, Yebin Seok, Seung Hyeok Chung, Hyewon Kim, Da Young Han, Dohyun Lee, Cheng Hyun Hwang, Eun Hye Park, Soo Young Koh, Jiwon Kim, Bohyun Nikas, Ilias P. Lee, Hyebin Hwang, Daehee Ryu, Han Suk Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title | Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title_full | Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title_fullStr | Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title_full_unstemmed | Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title_short | Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
title_sort | nicotinamide (niacin) supplement increases lipid metabolism and ros‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067146/ https://www.ncbi.nlm.nih.gov/pubmed/35278276 http://dx.doi.org/10.1002/1878-0261.13209 |
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