ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

novel chemotherapeutics with specific Wnt inhibitory effect. However, with such new
compounds the examination of the metabolic stability and pharmacokinetics are
necessary to be done before the engaging into preclinical studies.
Compound SC3 is an antibiotic substance known since 80’s of the last century but only
a little was reported about its molecular function within the cell. We identified this
compound in our high-throughput screen for modulators of the canonical Wnt signaling
pathway using Wnt/β-catenin responsive STF cells. The specificity and efficiency of SC3
was subsequently confirmed in several in vitro and in vivo assays including TOPFLASH
activity in luciferase assay and qRT-PCR in human colorectal cancer cell lines, double axis
formation assay in Xenopus embryos and intestinal tumor treatment in APC Min mice. Cells
cultivated with SC3 compound displayed reduced amount of β-catenin and in transient
transfections, TOPFLASH activity of several constitutively active mutants of β-catenin
was inhibited by the compound. These results suggest β-catenin-dependent effect of
SC3 molecule, although the exact mechanism of action has not been elucidated yet.
P36. PPARGAMMA IN COLON CANCER CELL DIFFERENTIATION AND DEATH INDUCED
BY FATTY ACID TREATMENT
Zuzana Tylichová 1,2 , Jiřina Hofmanová 1,2 , Pavel Krčmář 3 , Nicol Straková 1 , Alena Hyršlová
Vaculová 1 , Alois Kozubík 1,2
1
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech
Republic, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic;
2
Department of Experimental Biology, Faculty of Science, Masaryk University, 611 37
Brno, Czech Republic
3
Veterinary Research Institute,v.v.i. Brno, Czech Republic
tylichova@ibp.cz
Peroxisome proliferator-activated receptor γ (PPARγ) is nuclear receptor and transcription
factor that is involved in regulating glucose and lipid homeostasis, inflammation,
proliferation and differentiation. It is expressed mainly in colon and adipose tissues.
Dietary exogenous as well as endogenous fatty acids and their metabolites function as
PPARγ ligands and thus may affect many cellular events including cell cycle, fatty acid
transport and utilization and important signaling pathways. PPARγ is often mutated in
cancer cells which may contribute to cancer promotion and progression.
Molecular mechanisms of PPARγ action were investigated in colon adenocarcinoma
cell line HT-29 after treatment with short-chain fatty acid butyrate (NaBt) produced
by microbial fermentation of fibre in the colon and essential ω-3 polyunsaturated
docosahexaenoic fatty acid (DHA). Application of these coumpouds induced changes in
PPARγ expression on gene and protein levels and also its significant activation (luciferase
assay). The activation of PPARγ was additionaly supported using PI3K/Akt (Akt1/2)
inhibitor which increased differentiation as well as cell death. Caspases inhibitor (zVADfmk)
decreased paralelly PPARγ activation and cell differentiation but not apoptosis
which indicates non-apoptotic function of caspases. Using flow cytometry and methods
130 Analytical Cytometry VII