Format

Send to

Choose Destination
Cancer Sci. 2018 Nov 20. doi: 10.1111/cas.13886. [Epub ahead of print]

Increased NAD(H) pool promotes colon cancer progression by suppressing ROS level.

Author information

1
Department of Biochemistry and Department of Biomedical Sciences (BK21 Plus), Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
2
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
4
Biokogen Inc. F255, Korea National Food Cluster, 110 Dongchonje-gil, Wanggung-myeon, Iksan, Jeonbuk, 54576, Korea.
5
Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea.
6
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.
7
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
8
Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
9
Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea.

Abstract

Nicotinamide adenine dinucleotide (NAD) exists in a reduced form (NADH) and an oxidized form (NAD+). 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 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. This article is protected by copyright. All rights reserved.

KEYWORDS:

NAMPT ; Colon cancer; Inflammation; NAD(H) pool; Two-photon excitation fluorescence microscopy

PMID:
30457689
DOI:
10.1111/cas.13886
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center