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

ability to intercalate DNA although they possessed various affinity to DNA (in vitro
studies). Furthermore, hexyl-AcrDIM, the derivative with weak DNA-binding affinity, had
the most potent cytotoxic effect against several cancer cell lines.
In our present study, we have analyzed the accumulation and distribution of AcrDIMs in
mouse leukemic cell line L1210 to explain different cytotoxicity of analogs in the series.
We have monitored intracellular distribution of propyl- and hexyl-AcrDIM using an Amnis
ImageStream Imaging Flow Cytometer. Surprisingly, the colocalizations of AcrDIMs with
nucleic acids stain SytoRed 62 have shown that studied derivatives were not accumulated
in the nucleus even after long-term incubation (24 h). They were not localized in the
lysosomes as well (colocalization study of the derivatives with Monodansylcadaverine).
The fluorescence of propyl-AcrDIM was not overlaid with mitochondrial dye MitoRed,
but the derivative with the highest lipophilicity - hexyl-AcrDIM was partially accumulated
in the mitochondria (24 h).
Our results have confirmed that hexyl-AcrDIM, the most cytotoxic derivative of series,
was partially accumulated in the mitochondria. Mitochondrion, the energetic center of
cell and a key organelle in an intrinsic apoptotic pathway, is target of many anticancer
agents (Costantini et al., 2000). They may cause mitochondrial dysfunction and induce
oxidative stress in the cells. The level of superoxide radical in the cells treated with
hexyl-AcrDIM has increased several times, and block in synthetic phase of cell cycle
and apoptotic DNA-fragmentation has occurred. Nevertheless, cytotoxic mechanism of
hexyl-AcrDIM is not clear, yet. But the lipophilicity plays a crucial role in the distribution
of AcrDIMs and their following anticancer effect.
Acknowledgments
This work was supported by Structural Funds EU (ITMS: 26240220071) and the Grant
Agency VEGA of the Ministry of Education of the Slovak Republic (1/0672/11, 2/0177/11)
and it is result of the project implementation: TRANSMED 2, ITMS: 26240120030,
supported by the Research & Development Operational Programme funded by the ERDF.
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