The cytotoxicity of minority benzo[c]phenanthridine alkaloids

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Authors

SLUNSKÁ Zdenka SLANINOVÁ Iva ŠINKORA Jiří VLKOVÁ Marcela TÁBORSKÁ Eva

Year of publication 2006
Type Article in Proceedings
Conference Books of abstracts of CHEMISTRY, PHARMACOLOGY AND BIOSYNTHESIS OF ALKALOIDS
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords benzo[c]phenanthridine alkaloids
Description In this study we determined cytotoxicity of sanguirubine (SR), chelirubine (CHR), sanguilutine (SL), chelilutine (CHL) and macarpine (MA), minor occuring quaternary benzo[c]phenanthridine alkaloids (QBA), in comparison with the two best known QBA sanguinarine (SA) and chelerythrine (CHE). QBA are a small group of isoquinoline alkaloids that are distributed in a plant species of Papaveraceae, Fumariaceae and Rutaceae families. SA and CHE exhibit wide spectrum of biological activities, while the information about the biological effects of minority QBA is rare. Our attention was pointed to study antiproliferative and pro-apoptotic activities of QBA and their influence on cytoskeleton. The antiproliferative activity was assessed by MTT metabolic assay. One normal human (LEP), one hamster (V-79) and three human tumour cell lines (HeLa; HL-60; A-2780) were used as a model objects. Our results showed that IC50 values after 72 hours treatment of alkaloids were comparable with IC50 of routinely used cytostatics (i.e.: 0,01-1 microgram/ml). HL-60 was the most sensitive cell line while HeLa cells appeared to be the most resistant. For apoptosis detection morphology of nuclei of alkaloid treated HL-60 cells after DAPI staining was studied and flow cytometric analysis using Annexin V-FITC and propidium iodide was applied. All tested alkaloids appeared to be inductors of apoptosis at the concentration 1 microgram/ml. Based on our observations we concluded that alkaloids tested in this study show strong antiproliferative, proapoptotic effect and effect on cytoskeleton.
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