%0 Journal Article
%T Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level
%A Chan W. Kim
%A Chang W. Park
%A Gyesoon Yoon
%A Ji H. Shin
%A Jin©\Hak Jung
%A Jong L. Lee
%A Ki H. Kim
%A Kwan Y. Choi
%A Sang©\Yeob Kim
%A Seung©\Jae Myung
%A Sun M. Hong
%A Sung W. Hwang
%A Taejun Wang
%A Yeon©\Mi Ryu
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13886
%X 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 FK866, 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
%K colon cancer
%K inflammation
%K NAD(H) pool
%K nicotinamide phosphoribosyltransferase
%K two©\photon excitation fluorescence microscopy
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361564/