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

However, a precise mode of the regulation of 5-FU-elicited autophagy and its functional
role in general cytotoxic response of colon cancer cells as well as its relationship with
p53 signaling still remains poorly defined.
We investigated the ability of 5-FU to trigger autophagy in human colon cancer cells with
different p53 status, the kinetics of the response, and the essential molecules involved.
Using chemical inhibitors of autophagy (e.g. 3-methyladenine, bafilomycin A1) or specific
siRNAs against crucial autophagy regulators of the Atg family, we studied the functional
role of autophagy in modulation of the overall death response of colon cancer cells to
5-FU. The crosstalk of 5-FU-induced autophagy and apoptosis was also examined and
compared in cells with different status of p53.
We showed that the ability of 5-FU to trigger autophagic response was significantly
enhanced in colon cancer cells deficient for p53, which were simultaneously less
sensitive to 5-FU-induced apoptosis compared to their wt counterparts. Chemical
inhibitor-mediated blockage of autophagy in its early (3-MA) or later (bafilomycin
A1) stages resulted in suppression or stimulation of 5-FU-induced apoptosis and/or
overall death especially in p53-deficient colon cancer cells, respectively. At the same
time, siRNA-mediated silencing of selected Atg family regulators (e.g. Beclin 1, Atg7)
exerted weaker effects. In addition, inhibition of selected MAPKs impaired 5-FU-induced
autophagy preferentially in cells lacking p53.
Our results suggest that targetting autophagy could contribute to the modulation of the
general cytotoxic response to 5-FU especially in colon cancer cells with non-functional
p53.
This work was supported by the grants from IGA of the Ministry of Health of the Czech
republic No. NT11201-5, Ministry of Education, Youth and Sports of the Czech Republic,
European Regional Development Fund (CZ.1.07/2.3.00/20.0180).
P3. EFFECT OF HSP90 INHIBITION ON CELL CYCLE REGULATION VIA ITS CLIENT
PROTEINS
Ľubomír Čulka, Jaromír Mikeš, Lenka Kundeková, Peter Fedoročko
P. J. Šafárik University in Košice, Faculty of Science, Institute of Biology and Ecology,
Košice, Slovak Republic; lubo.culka@gmail.com
Heat shock protein 90 (HSP90) is an abundant protein crucial for many cellular processes.
It fulfils a protective function for the cell under stress conditions and it also plays an
essential role as molecular chaperone. In addition, HSP90 exerts its function via specific
subset of proteins called client proteins, as the HSP90 function is essential for their
conformational maturation and stability. Regulation of client proteins by the chaperone
plays a crucial role in processes such as cell cycle control, differentiation and apoptosis
(Mahalingam et al., 2009)
In cancer cells, HSP90 overexpression is regularly observed in many types of tumours
and its higher levels are typically associated with poorer prognosis and resistance to
Analytical Cytometry VII 89