The mechanism of the inhibitory action of lipopolysaccharide on anti-cancer drug-induced cell injury

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590404
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: AICHI MEDICAL UNIVERSITY
• Principal Investigator: YOKOCHI Takashi Aichi Medical University, Department of Microbiology and Immunology, Professor, 医学部, 教授 (20126915)
• Project Period (FY): 2005 – 2006
• Keywords: lipopolysaccharide / endotoxin / doxorubicin / p53 / macrophage / apoptosis / anti-cancer drug / DNA damage

Research Abstract

The effect of lipopolysaccharide (LPS) on doxorubicin (DXB)-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with LPS at 10ng/ml prevented DXB-induced cell death and the inhibition was roughly dependent on the concentration of LPS. The 1 h post-treatment of LPS also prevented DXB-induced cell death. LPS inhibited DNA fragmentation and caspase 3 activation in DXB-treated RAW 264.7 cells, suggesting the prevention of DXB-induced apoptosis. LPS did not significantly inhibit DXB-induced DNA damages detected by a single cell gel electrophoresis (comet) assay. LPS definitely inhibited the stabilization and nuclear translocation of p53 in DXB-treated RAW 264.7 cells. LPS as well as an inhibitor of p53 abolished DXB-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of DXB-induced apoptosis in RAW 264.7 cells by LPS.

Research Products

• [Journal Article] Lipopolysaccharide prevents apoptosis induced by brefeldin A, an endoplasmic reticulum stress agent, in RAW 264.7 cells (2006)
  • Author(s): Islam S et al.
  • Journal Title: Biochem Biophys Res Commun 340 Pages: 589-596
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock (2006)
  • Author(s): Ito H et al.
  • Journal Title: Lab Invest 86 Pages: 254-261
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of biological activities of Brucella melitensis lipopolysaccharide (2006)
  • Author(s): Tumurkhuu G et al.
  • Journal Title: Microbiol Immunol 50 Pages: 421-427
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide (2006)
  • Author(s): Hassan F et al.
  • Journal Title: BMC Cancer 6 Pages: 281
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Defective responsiveness of CD5+ B1 cells to lipopolysaccharide in cytokine production (2006)
  • Author(s): Koide N et al.
  • Journal Title: J End Res 12 Pages: 346-351
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice (2006)
  • Author(s): Yamaguchi K et al.
  • Journal Title: Biochim Biophys Acta 1762 Pages: 269-275
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Lipopolysaccharide prevents apoptosis induced by brefeldin A, an endoplasmic reticulum stress agent, in RAW 264.7 cells. (2006)
  • Author(s): Islam S, Hassan F, Tumurkhuu G, Ito H, Koide N, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Biochem Biophys Res Commun. 340 Pages: 589-96
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice. (2006)
  • Author(s): Yamaguchi K, Yu Z, Kumamoto H, Sugawara Y, Kawamura H, Takada H, Yokochi T, Sugawara S, Endo Y.
  • Journal Title: Biochim Biophys Acta. 1762 Pages: 269-75
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock. (2006)
  • Author(s): Ito H, Koide N, Hassan F, Islam S, Tumurkhuu G, Mori I, Yoshida T, Kakumu S, Moriwaki H, Yokochi T.
  • Journal Title: Lab Invest. 86 Pages: 254-61
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of biological activities of Brucella melitensis lipopolysaccharide. (2006)
  • Author(s): Tumurkhuu G, Koide N, Takahashi K, Hassan F, Islam S, Ito H, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Microbiol Immunol. 50 Pages: 421-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intracellular expression of toll-like receptor 4 in neuroblastoma cells and their unresponsiveness to lipopolysaccharide. (2006)
  • Author(s): Hassan F, Islam S, Tumurkhuu G, Naiki Y, Koide N, Mori I, Yoshida T, Yokochi T.
  • Journal Title: BMC Cancer. 6 Pages: 281
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A role of mitogen and stress-activated protein kinase 1/2 in survival of lipopolysaccharide-stimulated RAW 264.7 macrophages. (2005)
  • Author(s): Mu MM, Koide N, Hassan F, Islam S, Sugiyama T, Ito H, Mori I, Yoshida T, Yokochi T.
  • Journal Title: FEMS Immunol Med Microbiol. 43 Pages: 277-86
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Serum-dependent potentiation of lipopolysaccharide-induced nitric oxide production is mediated by the events after the transcription of inducible type of nitric oxide synthase. (2005)
  • Author(s): Zhang YH, Murphy WJ, Russell SW, Morrison DC, Koide N, Yoshida T, Yokochi T.
  • Journal Title: Cell Immunol. 234 Pages: 16-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lipopolysaccharide prevents doxorubicin-induced apoptosis in RAW 264.7 macrophage cells by inhibiting p53 activation. (2005)
  • Author(s): Hassan F, Islam S, Mu MM, Ito H, Koide N, Mori I, Yoshida T, Yokochi T.
  • Journal Title: Mol Cancer Res. 3 Pages: 373-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of extracellular signal-regulated kinase 1/2 augments nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells. (2005)
  • Author(s): Koide N, Ito H, Mu MM, Sugiyama T, Hassan F, Islam S, Mori I, Yoshida T, Yokochi T.
  • Journal Title: FEMS Immunol Med Microbiol. 45 Pages: 213-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Augmentation of lipopolysaccharide-induced nitric oxide production by alpha-galactosylceramide in mouse peritoneal cells. (2005)
  • Author(s): Ito H, Koide N, Morikawa A, Hassan F, Islam S, Tumurkhuu G, Mori I, Yoshida T, Kakumu S, Moriwaki H, Yokochi T.
  • Journal Title: J Endotoxin Res. 11 Pages: 213-9
  • Description: 「研究成果報告書概要(欧文)」より