Naslov
Induction of apoptosis of human tumor cells by 4, 9-diazapyrenium derivative (FDAP) and its affects on topoisomerase II action

Autori
Marczi, Saška ; Glavaš-Obrovac, Ljubica ; Karner, Ivan

Izvornik
Chemotherapy (Basel) (0009-3157) 51 (2005); 217-222

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
4; 9-Diazapyrenium derivatives; apoptosis; topoisomerase II

Sažetak
Background: 5, 10-Diphenyl-4, 9-dimethyl-4, 9-diazapyrenium hydrogensulfate (FDAP) is a newly synthesized DNA intercalator with strong antiproliferative activity against various human tumor cells. In this study, FDAP's potential to induce apoptosis in human pancreatic (MIAPaCa-2) and colon (CaCo-2) carcinoma cells and its effects on topoisomerase II activity were investigated. Methods: Cytotoxicity was analyzed using the MTT assay. Antiproliferative activity was measured via radioactive precursors incorporation assay. DNA fragmentation was analyzed by agarose gel electrophoresis. Apoptosis was detected using annexin-V-fluorescein. For screening of topoisomerase II-targeted effects of FDAP the cell-free assays were used. Results: FDAP in concentration of 10 μ M and 1 μ M caused a strong cytotoxic effect on MIAPaCa-2 cells, but a slight effect on WI38 cell's viability. Inhibition of the DNA, RNA and protein synthesis of the treated tumor cells was cell type dependent. DNA of the treated MIAPaCa-2 cells was fragmented. Phosphatidylserine externalization was detected in both investigated tumor cell lines. FDAP caused generation of DNA strand breaks due to interaction with human topoisomerase IIα . Conclusion: FDAP in 1 μ M concentration caused apoptotic cell death of treated tumor cells. FDAP stimulated a topoisomerase II-mediated DNA cleavage and could be considered topoisomerase II poison.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

POVEZANOST RADA