Role of short chain fatty acids and arachidonate metabolites in the regulation of proliferation and induction of apoptosis of gastrointestinal cells  Page description

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Details of project

  
Identifier
37401
Type K
Principal investigator Gálfi, Péter
Title in Hungarian A rövidszénláncú zsírsavak és egyes arachidonsav metabolitok szerepe a gastrointestinalis sejtek osztódásának szabályozásában és apoptosisának kialakulásában
Title in English Role of short chain fatty acids and arachidonate metabolites in the regulation of proliferation and induction of apoptosis of gastrointestinal cells
Panel Plant and animal breeding
Department or equivalent Department of Physiology and Biochemistry (Hungarian University of Agriculture and Life Sciences)
Participants Neogrády, Zsuzsa
Rimanóczy, Lászlóné
Starting date 2002-01-01
Closing date 2005-12-31
Funding (in million HUF) 12.271
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
Megállapítottuk, hogy az indometacin a HT29 sejtekből származó colorectalis adenocarcinoma sejtek esetében a butirát sejtosztódás gátló hatásával szemben rezisztenciát alakít ki, és ez a hatás nordihidrogvajaretsavval felfüggeszthető. Az indometacin hatása a butiráttal kezelt sejteknél abban nyilvánul meg, hogy a sejtkolóniák száma és nagysága növekszik, a Ki67 pozitív sejtek száma emelkedik, nő a H2O2 termelés, az NFkappaB aktiválódik, a COX-1 és a COX-2 expresszió egyaránt fokozódik és a butirát indukálta differenciáció gátlódik. Nordihidrogvajaretsav adása indometacin jelenlétében butiráttal kezelt sejteknél azt eredményezi, hogy a sejthalál jelentős mértékben fokozódik. E nem szteroid gyulladáscsökkentőnek azt a képességét, amely a butirát proliferációra gyakorolt gátló hatásával szemben érvényesül tumor sejteknél, mellékhatásként kell értékelni, mely főleg a colonban jelentkezik, ahol a butirát millimoláris koncentrációban van jelen.
Results in English
It was established that indomethacin increased the resistance of HT29-derived colon cancer cells to butyrate-mediated growth inhibition, and this effect of indomethacin was abrogated by nordihydroguaraetic acid. The effect of indomethacin on butyrate treated cells was manifested by increased numbers and larger colonies, nuclear accumulation of the proliferation marker Ki67, increase of H2O2 production, activation of NFkappaB, upregulation of both COX-1 and COX-2 and inhibition of butyrate-induced cell differentiation. Application of nordihydroguaraetic acid together with indomethacin to butyrate-treated cells, resulted in highly increased cell death induction. The ability of a nonsteroidal anti-inflammatory drug to counteract butyrate-mediated proliferation inhibition in tumour cells must be considered as a serious side effect, especially in the colon, wich is exposed to millimolar concentration of butyrate.
Full text http://real.mtak.hu/195/
Decision
Yes





 

List of publications

  
P. Galfi, Zs. Neogrady, A. Amberger, R. Margreiter, A. Csordas: Sensitization of colon cancer cell lines for histone deacetylase-mediated proliferation inhibition by combined application of indomethacin and NDGA, 7th International Symposium on Predictive Oncology & Intervention Strategies, February 7 to 10, 2004, Nice, France, Abstract 124, S-86, 2004
P. Galfi, J. Jakus, T. Molnar, Zs. Neogrady, A.Csordas: Effects of resveratrol, a polyphenolic phytostilbene, on ROI level and the type of cell death induced by histone deacetylase inhibitors, 16th International Symposium of the Journal of Steroid Biochemistry & Molecular Biology, Seefeld, Austria, 5-8 June 2004, 2004
P. Galfi, J. Jakus, T. Molnar, Zs. Neogrady, A. Csordas: Distinct forms of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A, EACR18, 18th Meeting of the EUROPEAN ASSOCIATION FOR CANCER RESEARCH, Innsbruck, Austria, 3-6 July, 2004, 2004
A. Csordas, Zs. Neogrady, T. Molnar, J. Jakus and P.Galfi: Divergent effects of resveratrol on ROI level and mode of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A, EACR18, 18th Meeting of the EUROPEAN ASSOCIATION FOR CANCER RESEARCH, Innsbruck, Austria, 3-6 July, 2004, 2004
P. Galfi, J. Jakus, T. Molnar, Zs. Neogrady, A. Csordas: Effects of resveratrol on the total radical level and mode of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A, 22nd International Conference on Polyphenols, ICP2004, Helsinki, Finland, 25-28 August 2004, 2004
M. Heitz, P. Galfi, A. Amberger, S. Neogrady, R. Margreiter, A. Csordas: COX-1 expression levels in colon cancer cell lines are altered in the presence of butyrate or indomethacin, EACR18, 18th Meeting of the EUROPEAN ASSOCIATION FOR CANCER RESEARCH, Innsbruck, Austria, 3-6 July, 2004, 2004
Gálfi, P., Neogrády, S., Csordás, A.: Apoptosis sensitivity is not correlated with sensitivity to proliferation inhibition by the histone deacetylase inhibitors butyrate and TSA., Cancer Letters, 2002
P. Galfi, J. Jakus, T. Molnar, Zs. Neogrady, A. Csordas: Divergent effects of resveratrol, a polyphenolic phytostilbene, on free radical levels any type of cell death induced by histone deacetylase inhibitors butyrate and trichostatin A, The Journal of Steroid Biochemistry and Molecular Biology, 2005
Galfi, P., Zs. Neogrady, A. Amberger, R. Margreiter, A. Csordas: Sensitisation of colon cancer cell lines to butyrate-mediated proliferation inhibition by combined application of indomethacin and NDGA, Cancer Detection and Prevention 29, 276-285., 2005
Csordas, A., J. Judit, T. Molnar, Zs. Neogrady, P. Galfi: NADPH oxidase-derived free radicals protect colon cancer cells from butyrate-induced cell death, P-48, Joint Annual Meeting of the ÖGBM, ÖGGGT, ÖGBT and ANGT, September 16th – 18th, 2005, Vienna, Austria, 2005
Csordas, A., J., Judit, V. Jenei, T. Molnar, Zs. Neogrady, P. Gálfi: Indomethacin attenuates sensitivity to butyrate and alters H2O2 and free radical levels in colon cancer cells, P-48, Joint Annual Meeting of the ÖGBM, ÖGGGT, ÖGBT and ANGT, September 16th – 18th, 2005, Vienna, Austria, 2005



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