Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level.

Autor: Hong SM; Department of Biochemistry and Department of Biomedical Sciences (BK21 Plus), Ajou University School of Medicine, Suwon, Korea., Hwang SW; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Wang T; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Park CW; Biokogen Inc. F255, Korea National Food Cluster, Iksan, Jeonbuk, Korea., Ryu YM; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea., Jung JH; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea., Shin JH; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Kim SY; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea., Lee JL; Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Kim CW; Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Yoon G; Department of Biochemistry and Department of Biomedical Sciences (BK21 Plus), Ajou University School of Medicine, Suwon, Korea., Kim KH; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea.; Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Myung SJ; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.; Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea., Choi KY; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2019 Feb; Vol. 110 (2), pp. 629-638. Date of Electronic Publication: 2018 Dec 27.
DOI: 10.1111/cas.13886
Abstrakt: 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.
(© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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