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Pregled bibliografske jedinice broj: 49860


Autori: Steiner-Biočić, Ivka; Glavaš-Obrovac, Ljubica; Karner, Ivan; Piantanida, Ivo; Žinić, Mladen; Pavelić, Krešimir; Pavelić, Jasminka
Naslov: 4,9-Diazapyrenium Dications Induce Apoptosis in Human Tumor Cells
Izvornik: Anticancer Research (0250-7005) 16 (1996); 3705-3708
Vrsta rada: članak
Ključne riječi: DNA intercalation; Antitumor agents; Tumor cells; Apoptosis
We investigated the antiproliferative effects of two planar 4,9-diazapyrenium hydrogenasulphates against human malignant MiaPaCa 2 (pancreatic carcinoma), Hep 2 (laryngeal carcinoma) and human normal fibroblasts (WI 38) cell lines. The tested compounds were very potent in inhibiting the growth of the treated cell lines. Treatment with molar concentrations of the substances (10-4 - 10-7M) caused growth inhibition by more than 50%. The morphological changes of treated cells were also observed. Cells became smaller, with condensed chromatin and fragmented nuclei, the characteristics of dying cells. The identification of DNA-fragmentation and the appearance of chromatin aggregation leads us to assume the tested substances induced apoptosis of the investigated tumor cell lines. DNA intercalating antitumor agents represent one of the most widely used classes of chemotherapeutic agents in clinical oncology. They have a multiplicity of effects on malignant cells. The different classes of DNA intercalating agents show that antitumor activity is associated with DNA binding affinity and slow drug dissociation rate. By intercalation into target cell DNA they cause damage to gene expression, along with antiproliferative and cytotoxic effects. Specific cyclic compounds have been demonstrated to trigger programmed cell death i.e. apoptosis. Among the recently studied intercalators are planar 2,7-diazapyrenium dications. They bind specifically to A- and/or T-rich single straanded oligonucleotides producing photocleavage under illumination with visible light. Surprisingly, synthetic isomeric 4,9-diazapyrenium dications have not been studied yet, although they posses more pronounced structural similarity than 2,7-isomers to the potent DNA intercalator ethidium bromide. Hence, the biological activity of 4,9-diazapyrenium dications may be anticipated. This paper describes the antiproliferative and cytotoxic effects of two 4,9 diazapyrenium hydrogenasulphates against MiaPaCa 2, Hep 2 and WI 38 cell lines.
Projekt / tema: 00980703, 00981103, 00981104, 127009
Izvorni jezik: ENG
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Kategorija: Znanstveni
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Google Scholar: 4,9-Diazapyrenium Dications Induce Apoptosis in Human Tumor Cells

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