PMID- 31991021 OWN - NLM STAT- MEDLINE DCOM- 20200422 LR - 20200422 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 111 IP - 4 DP - 2020 Apr TI - Theracurmin inhibits intestinal polyp development in Apc-mutant mice by inhibiting inflammation-related factors. PG - 1367-1374 LID - 10.1111/cas.14329 [doi] AB - Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well-known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc-mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10-20 microM Theracurmin for 24 hours reduced nuclear factor-kappaB (NF-kappaB) transcriptional activity in human colon cancer DLD-1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF-kappaB promoter transcriptional activity. As NF-kappaB is a regulator of inflammation-related factors, we next investigated the downstream targets of NF-kappaB: monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP-1 and IL-6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J-CAP-C study). CI - (c) 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Adachi, Saeko AU - Adachi S AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. AD - Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushuu University, Fukuoka, Japan. FAU - Hamoya, Takahiro AU - Hamoya T AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. FAU - Fujii, Gen AU - Fujii G AD - Central Radioisotope Division, National Cancer Center Research Institute, Tokyo, Japan. FAU - Narita, Takumi AU - Narita T AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. FAU - Komiya, Masami AU - Komiya M AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. FAU - Miyamoto, Shingo AU - Miyamoto S AD - Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan. FAU - Kurokawa, Yurie AU - Kurokawa Y AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. FAU - Takahashi, Maiko AU - Takahashi M AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. FAU - Takayama, Tetsuji AU - Takayama T AUID- ORCID: 0000-0002-0175-1573 AD - Department of Gastroenterology and Oncology, Faculty of Medicine Graduate School of Medical Sciences, University of Tokushima, Tokushima, Japan. FAU - Ishikawa, Hideki AU - Ishikawa H AD - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Tashiro, Kosuke AU - Tashiro K AD - Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushuu University, Fukuoka, Japan. FAU - Mutoh, Michihiro AU - Mutoh M AUID- ORCID: 0000-0003-2054-7655 AD - Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan. AD - Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan. LA - eng GR - MAFF-CPS-2016-1-1/The Ministry of Agriculture, Fishery and Forestry/ GR - 18ck0106271h0002/Japan Agency for Medical Research and Development/ PT - Journal Article DEP - 20200222 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Adenomatous Polyposis Coli Protein) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (adenomatous polyposis coli protein, mouse) RN - IT942ZTH98 (Curcumin) SB - IM MH - Adenomatous Polyposis Coli/drug therapy/genetics/pathology MH - Adenomatous Polyposis Coli Protein/*genetics MH - Animals MH - Carcinogenesis/drug effects MH - Chemokine CCL2/*genetics MH - Colorectal Neoplasms/*drug therapy/genetics/pathology MH - Curcumin/analogs & derivatives/*pharmacology MH - Disease Models, Animal MH - Gene Expression Regulation, Neoplastic/drug effects MH - HCT116 Cells MH - Humans MH - Inflammation/drug therapy/genetics/pathology MH - Interleukin-6/*genetics MH - Intestinal Polyps/drug therapy/genetics/pathology MH - Intestines/drug effects/pathology MH - Mice MH - NF-kappa B/genetics PMC - PMC7156816 OTO - NOTNLM OT - Theracurmin OT - colorectal cancer chemoprevention OT - curcumin OT - min mice OT - nuclear factor-kappaB COIS- The authors have no potential conflicts of interest to disclose. EDAT- 2020/01/29 06:00 MHDA- 2020/04/23 06:00 PMCR- 2020/04/01 CRDT- 2020/01/29 06:00 PHST- 2019/10/06 00:00 [received] PHST- 2020/01/18 00:00 [revised] PHST- 2020/01/21 00:00 [accepted] PHST- 2020/01/29 06:00 [pubmed] PHST- 2020/04/23 06:00 [medline] PHST- 2020/01/29 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - CAS14329 [pii] AID - 10.1111/cas.14329 [doi] PST - ppublish SO - Cancer Sci. 2020 Apr;111(4):1367-1374. doi: 10.1111/cas.14329. Epub 2020 Feb 22.