Open AccessIncreased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level
Author(s) -
Hong Sun M.,
Hwang Sung W.,
Wang Taejun,
Park Chang W.,
Ryu YeonMi,
Jung JinHak,
Shin Ji H.,
Kim SangYeob,
Lee Jong L.,
Kim Chan W.,
Yoon Gyesoon,
Kim Ki H.,
Myung SeungJae,
Choi Kwan Y.
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13886
Subject(s) - nad+ kinase , nicotinamide phosphoribosyltransferase , nicotinamide adenine dinucleotide , azoxymethane , reactive oxygen species , nicotinamide , chemistry , downregulation and upregulation , nicotinamide mononucleotide , cancer research , colorectal cancer , biochemistry , biology , cancer , microbiology and biotechnology , enzyme , gene , genetics
Nicotinamide adenine dinucleotide ( NAD ) exists in an oxidized form (NAD + ) and a reduced form (NADH). NAD + plays crucial roles in cancer metabolism, including in cellular signaling, energy production and redox regulation. However, it remains unclear whether NAD (H) pool size ( NAD + and NADH ) could be used as biomarker for colon cancer progression. Here, we showed that the NAD (H) pool size and NAD + / NADH ratio both increased during colorectal cancer ( CRC ) progression due to activation of the NAD + salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT). The NAMPT expression was upregulated in adenoma and adenocarcinoma tissues from CRC patients. The NADH fluorescence intensity measured by two‐photon excitation fluorescence ( TPEF ) microscopy was consistently increased in CRC cell lines, azoxymethane/dextran sodium sulfate (AOM/DSS)‐induced CRC tissues and tumor tissues from CRC patients. The increases in the NAD (H) pool inhibited the accumulation of excessive reactive oxygen species ( ROS) levels and FK 866, a specific inhibitor of NAMPT , treatment decreased the CRC nodule size by increasing ROS levels in AOM / DSS mice. Collectively, our results suggest that NAMPT ‐mediated upregulation of the NAD (H) pool protects cancer cells against detrimental oxidative stress and that detecting NADH fluorescence by TPEF microscopy could be a potential method for monitoring CRC progression.