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NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer

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Title
NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer
Author(s)
SM Hong; CW Park; SW Kim; YJ Nam; JH Yu; JH Shin; CH Yun; SH Im; KT Kim; YC Sung; KY Choi
Publication Date
2016-07
Journal
ONCOGENE, v.35, no.27, pp.3544 - 3554
Publisher
NATURE PUBLISHING GROUP
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in NAD+ biosynthesis. Although NAMPT has emerged as a critical regulator of metabolic stress, the underlying mechanisms by which it regulates metabolic stress in cancer cells have not been completely elucidated. In this study, we determined that breast cancer cells expressing a high level of NAMPT were resistant to cell death induced by glucose depletion. Furthermore, NAMPT inhibition suppressed tumor growth in vivo in a xenograft model. Under glucose deprivation conditions, NAMPT inhibition was found to increase the mitochondrial reactive oxygen species (ROS) level, leading to cell death. This cell death was rescued by treatment with antioxidants or NAD+. Finally, we showed that NAMPT increased the pool of NAD+ that could be converted to NADPH through the pentose phosphate pathway and inhibited the depletion of reduced glutathione under glucose deprivation. Collectively, our results suggest a novel mechanism by which tumor cells protect themselves against glucose deprivation-induced oxidative stress by utilizing NAMPT to maintain NADPH levels.
URI
https://pr.ibs.re.kr/handle/8788114/2742
ISSN
0950-9232
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
Files in This Item:
(2015)NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer.pdfDownload

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