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

36 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

Fingerprint

Minocycline
Mucositis
Fluorouracil
Chemotherapy
Poly(ADP-ribose) Polymerases
Heterografts
Drug Therapy
Enterocytes
Interleukin-1
Small Intestine
Tumors
Weight Loss
Diarrhea
Neoplasms
Anti-Inflammatory Agents
Up-Regulation
Body Weight
Wounds and Injuries
Therapeutics
Pharmaceutical Preparations

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

Cite this

Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model. / Huang, Tien-Yu; Chu, Heng-Cheng; Lin, Yi-Ling; Ho, Whae-Hong; Hou, Hsien-San; Chao, You-Chen; Liao, Ching-Len.

In: Biochemical and Biophysical Research Communications, Vol. 389, No. 4, 2009, p. 634-639.

Research output: Contribution to journalArticle

Huang, Tien-Yu ; Chu, Heng-Cheng ; Lin, Yi-Ling ; Ho, Whae-Hong ; Hou, Hsien-San ; Chao, You-Chen ; Liao, Ching-Len. / Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 389, No. 4. pp. 634-639.
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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. {\circledC} 2009 Elsevier Inc. All rights reserved.",
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author = "Tien-Yu Huang and Heng-Cheng Chu and Yi-Ling Lin and Whae-Hong Ho and Hsien-San Hou and You-Chen Chao and Ching-Len Liao",
note = "被引用次數:20 Export Date: 22 March 2016 CODEN: BBRCA 通訊地址: Liao, C.-L.; Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan; 電子郵件: chnglen@ms1.hinet.net 化學物質/CAS: fluorouracil, 51-21-8; inducible nitric oxide synthase, 501433-35-8; minocycline, 10118-90-8, 11006-27-2, 13614-98-7; poly(adenosine diphosphate ribose), 26656-46-2; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Cytokines; Fluorouracil, 51-21-8; Minocycline, 10118-90-8; Nitric Oxide Synthase Type II, 1.14.13.39; Nos2 protein, mouse, 1.14.13.39; Poly(ADP-ribose) Polymerases, 2.4.2.30; poly(ADP-ribose)polymerase-1, mouse, 2.4.2.30 製造商: Sigma Aldrich 參考文獻: Benson III, A.B., Ajani, J.A., Catalano, R.B., Engelking, C., Kornblau, S.M., Martenson Jr., J.A., McCallum, R., Wadler, S., Recommended guidelines for the treatment of cancer treatment-induced diarrhea (2004) J. Clin. Oncol., 22, pp. 2918-2926; Efficacy of adjuvant fluorouracil and folinic acid in colon cancer, International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators (1995) Lancet, 345, pp. 939-944; Bowen, J.M., Gibson, R.J., Cummins, A.G., Keefe, D.M., Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage (2006) Support. Care Cancer, 14, pp. 713-731; Pritchard, D.M., Potten, C.S., Hickman, J.A., The relationships between p53-dependent apoptosis, inhibition of proliferation, and 5-fluorouracil-induced histopathology in murine intestinal epithelia (1998) Cancer Res., 58, pp. 5453-5465; Sonis, S.T., The pathobiology of mucositis (2004) Nat. Rev. Cancer, 4, pp. 277-284; Leitao, R.F., Ribeiro, R.A., Bellaguarda, E.A., Macedo, F.D., Silva, L.R., Oria, R.B., Vale, M.L., Brito, G.A., Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster (2007) Cancer Chemother. Pharmacol., 59, pp. 603-612; Huang, F.S., Kemp, C.J., Williams, J.L., Erwin, C.R., Warner, B.W., Role of epidermal growth factor and its receptor in chemotherapy-induced intestinal injury (2002) Am. J. Physiol. Gastrointest. Liver Physiol., 282, pp. G432-G442; Farrell, C.L., Bready, J.V., Rex, K.L., Chen, J.N., DiPalma, C.R., Whitcomb, K.L., Yin, S., Lacey, D.L., Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality (1998) Cancer Res., 58, pp. 933-939; Sapadin, A.N., Fleischmajer, R., Tetracyclines: nonantibiotic properties and their clinical implications (2006) J. Am. Acad. Dermatol., 54, pp. 258-265; Sriram, K., Miller, D.B., O'Callaghan, J.P., Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha (2006) J. Neurochem., 96, pp. 706-718; Cata, J.P., Weng, H.R., Dougherty, P.M., The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats (2008) Brain Res., 1229, pp. 100-110; Amin, A.R., Attur, M.G., Thakker, G.D., Patel, P.D., Vyas, P.R., Patel, R.N., Patel, I.R., Abramson, S.B., A novel mechanism of action of tetracyclines: effects on nitric oxide synthases (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 14014-14019; Rifkin, B.R., Vernillo, A.T., Golub, L.M., Blocking periodontal disease progression by inhibiting tissue-destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs (1993) J. Periodontol., 64, pp. 819-827; Zhu, S., Stavrovskaya, I.G., Drozda, M., Kim, B.Y., Ona, V., Li, M., Sarang, S., Friedlander, R.M., Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice (2002) Nature, 417, pp. 74-78; Chen, M., Ona, V.O., Li, M., Ferrante, R.J., Fink, K.B., Zhu, S., Bian, J., Friedlander, R.M., Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease (2000) Nat. Med., 6, pp. 797-801; Alano, C.C., Kauppinen, T.M., Valls, A.V., Swanson, R.A., Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 9685-9690; Kurita, A., Kado, S., Kaneda, N., Onoue, M., Hashimoto, S., Yokokura, T., Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats (2000) Cancer Chemother. Pharmacol., 46, pp. 211-220; Huang, T.Y., Chu, H.C., Lin, Y.L., Lin, C.K., Hsieh, T.Y., Chang, W.K., Chao, Y.C., Liao, C.L., Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases (2009) Toxicol. Appl. Pharmacol., 237, pp. 69-82; Cross, R.K., Wilson, K.T., Nitric oxide in inflammatory bowel disease (2003) Inflamm. Bowel Dis., 9, pp. 179-189; Aguilar-Quesada, R., Munoz-Gamez, J.A., Martin-Oliva, D., Peralta-Leal, A., Quiles-Perez, R., Rodriguez-Vargas, J.M., de Almodovar, M.R., Oliver, F.J., Modulation of transcription by PARP-1: consequences in carcinogenesis and inflammation (2007) Curr. Med. Chem., 14, pp. 1179-1187; Orsucci, D., Mancuso, M., Siciliano, G., Mitochondria, oxidative stress and PARP-1 network: a new target for neuroprotective effects of tetracyclines? (2008) J. Physiol., 586, pp. 2427-2428; Di Paola, R., Mazzon, E., Xu, W., Genovese, T., Ferrraris, D., Muia, C., Crisafulli, C., Cuzzocrea, S., Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock (2005) Eur. J. Pharmacol., 527, pp. 163-171; Martinez, J.A., Williams, C.S., Amann, J.M., Ellis, T.C., Moreno-Miralles, I., Washington, M.K., Gregoli, P., Hiebert, S.W., Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis (2006) Gastroenterology, 131, pp. 579-588; Chu, H.C., Lin, Y.L., Sytwu, H.K., Lin, S.H., Liao, C.L., Chao, Y.C., Effects of minocycline on Fas-mediated fulminant hepatitis in mice (2005) Br. J. Pharmacol., 144, pp. 275-282; Frazier, J.L., Wang, P.P., Case, D., Tyler, B.M., Pradilla, G., Weingart, J.D., Brem, H., Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma (2003) J. Neurooncol., 64, pp. 203-209; Saikali, Z., Singh, G., Doxycycline and other tetracyclines in the treatment of bone metastasis (2003) Anticancer Drugs, 14, pp. 773-778",
year = "2009",
doi = "10.1016/j.bbrc.2009.09.041",
language = "English",
volume = "389",
pages = "634--639",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier B.V.",
number = "4",

}

TY - JOUR

T1 - Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model

AU - Huang, Tien-Yu

AU - Chu, Heng-Cheng

AU - Lin, Yi-Ling

AU - Ho, Whae-Hong

AU - Hou, Hsien-San

AU - Chao, You-Chen

AU - Liao, Ching-Len

N1 - 被引用次數:20 Export Date: 22 March 2016 CODEN: BBRCA 通訊地址: Liao, C.-L.; Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan; 電子郵件: chnglen@ms1.hinet.net 化學物質/CAS: fluorouracil, 51-21-8; inducible nitric oxide synthase, 501433-35-8; minocycline, 10118-90-8, 11006-27-2, 13614-98-7; poly(adenosine diphosphate ribose), 26656-46-2; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Cytokines; Fluorouracil, 51-21-8; Minocycline, 10118-90-8; Nitric Oxide Synthase Type II, 1.14.13.39; Nos2 protein, mouse, 1.14.13.39; Poly(ADP-ribose) Polymerases, 2.4.2.30; poly(ADP-ribose)polymerase-1, mouse, 2.4.2.30 製造商: Sigma Aldrich 參考文獻: Benson III, A.B., Ajani, J.A., Catalano, R.B., Engelking, C., Kornblau, S.M., Martenson Jr., J.A., McCallum, R., Wadler, S., Recommended guidelines for the treatment of cancer treatment-induced diarrhea (2004) J. Clin. Oncol., 22, pp. 2918-2926; Efficacy of adjuvant fluorouracil and folinic acid in colon cancer, International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators (1995) Lancet, 345, pp. 939-944; Bowen, J.M., Gibson, R.J., Cummins, A.G., Keefe, D.M., Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage (2006) Support. Care Cancer, 14, pp. 713-731; Pritchard, D.M., Potten, C.S., Hickman, J.A., The relationships between p53-dependent apoptosis, inhibition of proliferation, and 5-fluorouracil-induced histopathology in murine intestinal epithelia (1998) Cancer Res., 58, pp. 5453-5465; Sonis, S.T., The pathobiology of mucositis (2004) Nat. Rev. Cancer, 4, pp. 277-284; Leitao, R.F., Ribeiro, R.A., Bellaguarda, E.A., Macedo, F.D., Silva, L.R., Oria, R.B., Vale, M.L., Brito, G.A., Role of nitric oxide on pathogenesis of 5-fluorouracil induced experimental oral mucositis in hamster (2007) Cancer Chemother. Pharmacol., 59, pp. 603-612; Huang, F.S., Kemp, C.J., Williams, J.L., Erwin, C.R., Warner, B.W., Role of epidermal growth factor and its receptor in chemotherapy-induced intestinal injury (2002) Am. J. Physiol. Gastrointest. Liver Physiol., 282, pp. G432-G442; Farrell, C.L., Bready, J.V., Rex, K.L., Chen, J.N., DiPalma, C.R., Whitcomb, K.L., Yin, S., Lacey, D.L., Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality (1998) Cancer Res., 58, pp. 933-939; Sapadin, A.N., Fleischmajer, R., Tetracyclines: nonantibiotic properties and their clinical implications (2006) J. Am. Acad. Dermatol., 54, pp. 258-265; Sriram, K., Miller, D.B., O'Callaghan, J.P., Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha (2006) J. Neurochem., 96, pp. 706-718; Cata, J.P., Weng, H.R., Dougherty, P.M., The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats (2008) Brain Res., 1229, pp. 100-110; Amin, A.R., Attur, M.G., Thakker, G.D., Patel, P.D., Vyas, P.R., Patel, R.N., Patel, I.R., Abramson, S.B., A novel mechanism of action of tetracyclines: effects on nitric oxide synthases (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 14014-14019; Rifkin, B.R., Vernillo, A.T., Golub, L.M., Blocking periodontal disease progression by inhibiting tissue-destructive enzymes: a potential therapeutic role for tetracyclines and their chemically-modified analogs (1993) J. Periodontol., 64, pp. 819-827; Zhu, S., Stavrovskaya, I.G., Drozda, M., Kim, B.Y., Ona, V., Li, M., Sarang, S., Friedlander, R.M., Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice (2002) Nature, 417, pp. 74-78; Chen, M., Ona, V.O., Li, M., Ferrante, R.J., Fink, K.B., Zhu, S., Bian, J., Friedlander, R.M., Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease (2000) Nat. Med., 6, pp. 797-801; Alano, C.C., Kauppinen, T.M., Valls, A.V., Swanson, R.A., Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 9685-9690; Kurita, A., Kado, S., Kaneda, N., Onoue, M., Hashimoto, S., Yokokura, T., Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats (2000) Cancer Chemother. Pharmacol., 46, pp. 211-220; Huang, T.Y., Chu, H.C., Lin, Y.L., Lin, C.K., Hsieh, T.Y., Chang, W.K., Chao, Y.C., Liao, C.L., Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases (2009) Toxicol. Appl. Pharmacol., 237, pp. 69-82; Cross, R.K., Wilson, K.T., Nitric oxide in inflammatory bowel disease (2003) Inflamm. Bowel Dis., 9, pp. 179-189; Aguilar-Quesada, R., Munoz-Gamez, J.A., Martin-Oliva, D., Peralta-Leal, A., Quiles-Perez, R., Rodriguez-Vargas, J.M., de Almodovar, M.R., Oliver, F.J., Modulation of transcription by PARP-1: consequences in carcinogenesis and inflammation (2007) Curr. Med. Chem., 14, pp. 1179-1187; Orsucci, D., Mancuso, M., Siciliano, G., Mitochondria, oxidative stress and PARP-1 network: a new target for neuroprotective effects of tetracyclines? (2008) J. Physiol., 586, pp. 2427-2428; Di Paola, R., Mazzon, E., Xu, W., Genovese, T., Ferrraris, D., Muia, C., Crisafulli, C., Cuzzocrea, S., Treatment with PARP-1 inhibitors, GPI 15427 or GPI 16539, ameliorates intestinal damage in rat models of colitis and shock (2005) Eur. J. Pharmacol., 527, pp. 163-171; Martinez, J.A., Williams, C.S., Amann, J.M., Ellis, T.C., Moreno-Miralles, I., Washington, M.K., Gregoli, P., Hiebert, S.W., Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis (2006) Gastroenterology, 131, pp. 579-588; Chu, H.C., Lin, Y.L., Sytwu, H.K., Lin, S.H., Liao, C.L., Chao, Y.C., Effects of minocycline on Fas-mediated fulminant hepatitis in mice (2005) Br. J. Pharmacol., 144, pp. 275-282; Frazier, J.L., Wang, P.P., Case, D., Tyler, B.M., Pradilla, G., Weingart, J.D., Brem, H., Local delivery of minocycline and systemic BCNU have synergistic activity in the treatment of intracranial glioma (2003) J. Neurooncol., 64, pp. 203-209; Saikali, Z., Singh, G., Doxycycline and other tetracyclines in the treatment of bone metastasis (2003) Anticancer Drugs, 14, pp. 773-778

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - 5-Fluorouracil

KW - Chemotherapy

KW - Minocycline

KW - Mucositis

KW - fluorouracil

KW - inducible nitric oxide synthase

KW - interleukin 1beta

KW - minocycline

KW - nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1

KW - poly(adenosine diphosphate ribose)

KW - tumor necrosis factor alpha

KW - animal cell

KW - animal experiment

KW - animal model

KW - animal tissue

KW - antineoplastic activity

KW - article

KW - body weight

KW - cell proliferation

KW - colon cancer

KW - controlled study

KW - diarrhea

KW - disease severity

KW - drug effect

KW - drug potentiation

KW - enzyme activity

KW - in vitro study

KW - intestine villus

KW - male

KW - mouse

KW - mucosa inflammation

KW - nonhuman

KW - priority journal

KW - protein expression

KW - small intestine disease

KW - small intestine mucositis

KW - treatment response

KW - upregulation

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Antimetabolites, Antineoplastic

KW - Apoptosis

KW - Cell Proliferation

KW - Cytokines

KW - Disease Models, Animal

KW - Fluorouracil

KW - Intestine, Small

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Neoplasms

KW - Nitric Oxide Synthase Type II

KW - Poly(ADP-ribose) Polymerases

KW - Xenograft Model Antitumor Assays

KW - Mus

U2 - 10.1016/j.bbrc.2009.09.041

DO - 10.1016/j.bbrc.2009.09.041

M3 - Article

VL - 389

SP - 634

EP - 639

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -