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

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

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Effects of studied newly synthesized PDMP derivatives were dependent on their chemical<br />

structure and duration of cell cultivation. Several derivatives were able to change<br />

Ca 2+ transport already after 15 minutes of cultivation, but their effect of cell viability<br />

manifested only after 12 h of cultivation. Activity of GlcCer synthase was affected in case<br />

of 4 from 12 studied compounds after longer cultivation, but was not in relation with<br />

changes in calcium transport and cell viability.<br />

Acknowledgement<br />

This work was supported by grant agency VEGA No. 01/0471/11 and 01/0441/11<br />

References:<br />

1. Hakomori, S. and Igarashi, Y. (1993) Adv. Lipid Res. 23, 147–162<br />

2. Lahiri, S. and Futerman, A. H. (2007) Cell. Mol. Life Sci. 64 (2007) 2270 – 2284<br />

P27. DOCOSAHEXAENOIC ACID EFFECTIVELY STIMULATES TRAIL-INDUCED APOPTOSIS<br />

OF COLON CANCER CELLS AT THE LEVEL OF MITOCHONDRIA<br />

Belma Skender 1, 2 , Björn Kruspig 3 , Vladimir Gogvadze 3 , Jiřina Hofmanová 1, 2 , Alois<br />

Kozubík 1, 2 , Boris Zhivotovsky 3 , Alena Hyršlová Vaculová 1<br />

1<br />

Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech<br />

Republic, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic;<br />

2<br />

Department of Animal Physiology and Immunology, Faculty of Science, Masaryk<br />

University, Terezy Novákové 64, 621 00 Brno, Czech Republic<br />

3<br />

Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box<br />

210, Stockholm, SE-171 77 Sweden<br />

belma@ibp.cz, vaculova@ibp.cz<br />

Docosahexaenoic acid (DHA), an essential n-3 polyunsaturated fatty acid, is known for<br />

its beneficial effect in a wide variety of diseases ranging from autoimmune disorders<br />

to several types of malignancies including colorectal cancer. During carcinogenesis,<br />

mitochondria-dependent apoptotic pathways are very frequently suppressed, which<br />

results in attenuation of cell death and enhanced proliferation. Mitochondria belong<br />

to the subcellular sites where n-3 fatty acids are rapidly incorporated. DHA containing<br />

six double bonds causes cardiolipin structural changes and increases mitochondrial<br />

membrane fatty acids unsaturation, their susceptibility to oxidative stress and alters<br />

membrane barrier properties. We hypothesize that DHA might facilitate the toxic effects<br />

of certain antitumour agents, which could directly and specifically reinforce apoptosis in<br />

cancer cells. Our aim was to elucidate a potential sensitizing effect of DHA on apoptosis<br />

induced by a cytokine of the tumor necrosis factor (TNF) family - TRAIL (TNF-related<br />

apoptosis inducing ligand) in colon cancer cells. TRAIL has been shown to selectively<br />

induce apoptosis in tumor, but not in normal cells. However, many tumor cells may still<br />

exhibit a TRAIL-resistant phenotype, which is currently a major obstacle in TRAIL-based<br />

therapy.<br />

Here, we demonstrate that DHA is capable to increase significantly apoptosis induced<br />

by this cytokine and highlight the importance of the mitochondrial apoptotic pathway in<br />

Analytical Cytometry VII 119

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