Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model

Tien-Yu Huang, Heng-Cheng Chu, Yi-Ling Lin, Whae-Hong Ho, Hsien-San Hou, You-Chen Chao, Ching-Len Liao

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Minocycline exerts anti-inflammatory and anti-apoptotic effects distinct from its antimicrobial function. In this study we investigated the effect of this drug on chemotherapy-induced gut damage. Body weight loss results, diarrhea scores, and villi measurements showed that minocycline attenuated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU). Minocycline repressed the expression of TNF-α, IL-1β, and iNOS, decreased the apoptotic index, and inhibited poly(ADP-ribose) polymerase-1 (PARP-1) activity in the mouse small intestine. In vitro experiments showed that minocycline suppressed the upregulation of PARP-1 activity in enterocyte IEC-6 cells treated with 5-FU. In addition, minocycline treatment appeared to enhance the antitumor effects of 5-FU in tumor CT-26 xenograft mice. Our results indicate that minocycline protects mice from gut injury induced by 5-FU and enhances the antitumor effects of 5-FU in xenograft mice. These observations suggest that minocycline treatment may benefit patients undergoing standard cancer chemotherapy by alleviating chemical-associated intestinal mucositis. © 2009 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)634-639
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume389
Issue number4
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • 5-Fluorouracil
  • Chemotherapy
  • Minocycline
  • Mucositis
  • fluorouracil
  • inducible nitric oxide synthase
  • interleukin 1beta
  • minocycline
  • nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1
  • poly(adenosine diphosphate ribose)
  • tumor necrosis factor alpha
  • animal cell
  • animal experiment
  • animal model
  • animal tissue
  • antineoplastic activity
  • article
  • body weight
  • cell proliferation
  • colon cancer
  • controlled study
  • diarrhea
  • disease severity
  • drug effect
  • drug potentiation
  • enzyme activity
  • in vitro study
  • intestine villus
  • male
  • mouse
  • mucosa inflammation
  • nonhuman
  • priority journal
  • protein expression
  • small intestine disease
  • small intestine mucositis
  • treatment response
  • upregulation
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimetabolites, Antineoplastic
  • Apoptosis
  • Cell Proliferation
  • Cytokines
  • Disease Models, Animal
  • Fluorouracil
  • Intestine, Small
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms
  • Nitric Oxide Synthase Type II
  • Poly(ADP-ribose) Polymerases
  • Xenograft Model Antitumor Assays
  • Mus

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