title: Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development.
abstract: The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU-induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-κB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-κB and HAT activation.
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kai
authors.affiliation: Department of Pharmacology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Oguchi
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Tabata
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Miyabi
authors.initials: M
authors.lastname: Yaegashi
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yumoto
authors.affiliation: Department of Pharmacology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D054360:Chemokine CXCL1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D044683:Colon, Descending / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D019587:Dietary Supplements; D050881:E1A-Associated p300 Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005472:Fluorouracil / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012720:Severity of Illness Index; D046509:Tissue Culture Techniques
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D003474:Curcumin; D005472:Fluorouracil