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Review Article

Journal of Digestive Cancer Research 2016; 4(2): 64-76

Published online December 31, 2016

© Korean Society of Gastrointestinal Cancer

Prospective Targets for Colon Cancer Prevention: from Basic Research, Epidemiology and Clinical Trial


Shingo Miyamoto1, Masaru Terasaki2, Rikako Ishigamori3, Gen Fujii4, Michihiro Mutoh1,4*



1Epidemiology and Prevention Division, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo,;
2School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Ishikari-Tobetsu, Hokkaido;
3Central Animal Division, 4Carcinogenesis and Cancer Prevention Division, National Cancer Center Research Institute,
National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan

Abstract

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor- &B (NF-қB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-қB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

KeywordsColon cancer Chemoprevention TCF/LEF NF-қB and NRF2

Article

Review Article

Journal of Digestive Cancer Research 2016; 4(2): 64-76

Published online December 31, 2016

Copyright © Korean Society of Gastrointestinal Cancer Research.

Prospective Targets for Colon Cancer Prevention: from Basic Research, Epidemiology and Clinical Trial

Shingo Miyamoto1, Masaru Terasaki2, Rikako Ishigamori3, Gen Fujii4, Michihiro Mutoh1,4*

1Epidemiology and Prevention Division, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo,;
2School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Ishikari-Tobetsu, Hokkaido;
3Central Animal Division, 4Carcinogenesis and Cancer Prevention Division, National Cancer Center Research Institute,
National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan

Abstract

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor- &B (NF-қB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-қB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

Keywords: Colon cancer, Chemoprevention, TCF/LEF, NF-қ,B and NRF2

Journal Info

JDCR
Vol.12 No.1
April 20, 2024
eISSN : 2950-9505
pISSN : 2950-9394
Frequency: Triannual

open access

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Journal of Digestive Cancer Research

eISSN 2950-9505
pISSN 2950-9394

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