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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

Authors
 Minsun Jung  ;  Kyung-Min Lee  ;  Yebin Im  ;  Seung Hyeok Seok  ;  Hyewon Chung  ;  Da Young Kim  ;  Dohyun Han  ;  Cheng Hyun Lee  ;  Eun Hye Hwang  ;  Soo Young Park  ;  Jiwon Koh  ;  Bohyun Kim  ;  Ilias P Nikas  ;  Hyebin Lee  ;  Daehee Hwang  ;  Han Suk Ryu 
Citation
 MOLECULAR ONCOLOGY, Vol.16(9) : 1795-1815, 2022-05 
Journal Title
MOLECULAR ONCOLOGY
ISSN
 1574-7891 
Issue Date
2022-05
MeSH
Animals ; Apoptosis ; Cell Line, Tumor ; Drug Repositioning ; Humans ; Lipid Metabolism ; Mice ; Niacin* / pharmacology ; Niacin* / therapeutic use ; Niacinamide / pharmacology ; Niacinamide / therapeutic use ; Reactive Oxygen Species / metabolism ; Triple Negative Breast Neoplasms* / pathology
Keywords
metabolism ; nicotinamide ; organoids ; proteogenomics ; reactive oxygen species ; triple negative breast neoplasms.
Abstract
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.
Files in This Item:
T202201927.pdf Download
DOI
10.1002/1878-0261.13209
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Jung, Minsun(정민선)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188679
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