Naslov
In vitro cytotoxicity of three 4, 9-diazapyrenium hydrogensulphate derivatives on different human tumor cell lines

Autori
Roknić, Saška ; Steiner-Biočić, Ivka ; Glavaš-Obrovac, Ljubica ; Karner, Ivan ; Piantanida, Ivo ; Žinić, Mladen ; Pavelić, Krešimir

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Godišnji sastanak hrvatskih biokemičara / Glavaš-Obrovac, Ljubica - Osijek : Hrvatsko biokemijsko društvo, 1998

Skup
Godišnji sastanak hrvatskih biokemičara s međunarodnim sudjelovanjem

Mjesto i datum
Osijek, Hrvatska, 17.09.1998. - 20.09.1998

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
4; 9-diazapyrenium; tumor cells; antitumor effect

Sažetak
4, 9-diazapyrenium derivatives are newly synthesized DNA-intercalative substances. In this study, three 4, 9-diazapyrenium hydrogensulphate derivatives: 5, 10-diphenyl-4, 9-dimethyl-4, 9-diazapyrenium hydrogensulphate (FDAP), 4, 9-dimethyl-4, 9-diazapyrenium hydrogensulphate (GDAP) and 2, 4, 7, 9-tetramethyl-4, 9-diazapyrenium hydrogensulphate (MDAP) were assayed for their biological effects in vitro on five human cell lines (MiaPaCa2 - pancreatic carcinoma, SKBr3 - breast carcinoma, HeLa - cervical and two colon carcinomas - CaCo2, SW620). Cytotoxic effects of 4, 9-diazapyreniums on cell growth and viability were determined using the tetrazolium dye (MTT) assay and by radiolabeled [3H]-thymidine incorporation studies. Potent growth inhibitory effect depended on the tumor cell line type and concentration (10-4 - 10-7 M) of substances. The best was observed on SKBr3 cells for FDAP and MDAP, and on SW620 cells for GDAP. The extent of DNA fragmentation was analysed by 1, 5% agarose gel electrophoresis. The results show fragmentation of MiaPaCa2 DNA treated with MDAP (10-6M), and HeLa DNA treated with GDAP (10-6M) in comparison with nontreated MiaPaCa2 and HeLa cells which DNAs were not fragmented. The expression of c-myc oncogene and p53 tumor supressor gene products was examined in SW620, CaCo2 and MiaPaCa2 cells treated with MDAP and GDAP (10-4M for 24 hours). The morphological changes depended on the type of the cell line. Cell death was accompanied by reduced cell volume, round cell shape, internucleosomal DNA fragmentation of treated cells, condensed chromatin - characteristics which pointed to apoptosis as possible mechanism of cell death.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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