gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Antiproliferative Effect of Telmisartan via PPARγ-Activation in Human Colon Cancer Cells

Meeting Abstract

  • Lucas Dong-Gun Lee - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin
  • Benjamin Mafura - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin
  • Sonja Dullat - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin
  • Johannes Christian Lauscher - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin
  • Heinz Joachim Buhr - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin
  • Jörg-Peter Ritz - Charité Campus Benjamin Franklin, Klinik für Allgemein-, Gefäß- und Thoraxchirurgie, Berlin
  • Jörn Gröne - Chirurgische Klinik I, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Allgemeinchirurgie, Berlin

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch352

DOI: 10.3205/11dgch352, URN: urn:nbn:de:0183-11dgch3524

Published: May 20, 2011

© 2011 Lee et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Telmisartan, an AT1-Receptor-Antagonist for essential hypertension therapy, also shows partial Peroxisom Proliferator Activated Receptor γ (PPARγ) activation in preadipocytes with metabolic effects. In tumor cells, PPARγ activation leads to apoptosis and cell cycle inhibition. This study was to investigate the potential antiproliferative effect of Telmisartan by activating PPARγ in colon cancer cells.

Materials and methods: Human colon cancer cells (HT29 and SW620) were either incubated with Telmisartan (0,2-5,0µM) or the full agonist Pioglitazon (25.0 µM) as positive control for 24-72h (negative control: DMSO). Before incubation, the qualitative proof of PPARγ1 and PPARγ2 has been done by RT-PCR. The mRNA regulation of the target genes PPARγ2 and Cystatin A under the respective incubation has been measured by the means of qRT-PCR (housekeeping gene: bActin). Phenotypical changes were quantitatively determined by MTT Proliferations Assay. Apoptosis was determined by the Caspase-3/7 Assay. Statistic evaluation with PASW 18.0.

Results: PPARγ1 and PPARγ2 are expressed in HT29 and SW620. Pioglitazone inhibits proliferation after 72h in HT29 (∆ 17.48%; p<0,005) and in SW620 (∆ 22.36%; p<0,005). Telmisartan showed already at 0,2µM a proliferation inhibition of 20,06% in HT29 (p<0,005) and 18.33% in SW620 (p<0,005) (Figure 1 [Fig. 1]). Pioglitazone and Telmisartan downregulated PPARγ2mRNA in HT29 (fold change 0.2 and 0,66 respectively; n.s.) and in SW620 (fold change 0.82 and 0,68 respectively; n.s.) while upregulating CystatinA in HT29 (fold change 4.24 and 2,15 respectively; n.s.) and in SW620 (fold change 2.35 and 3,71 respectively; n.s.). Pioglitazone and Telmisartan increased the Caspase-3/7-acvtivity in HT29 and SW620 (p<0,005).

Conclusion: 1) The antihypertensive Telmisartan shows at therapeutic serum concentrations antiproliferative effects in colon cancer cells. 2) As a well-known partial PPARγ agonist, it shows an at least equivalent inhibiting effect despite comparatively smaller concentration compared to the full agonist Pioglitazone. 3) These results imply an antiproliferative effect by PPARγ1-activation.