Antiproliferative activities of selected benzo[c]phenanthridine alkaloids.

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Authors

SLUNSK Zdenka SLANINOVÁ Iva ŠINKORA Jiří VLKOVÁ Marcela TBORSKÁ Eva

Year of publication 2005
Type Article in Proceedings
Conference Biomedical Papers
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords benzo[c]phenanthridine alkaloid; cytotoxicity; apoptosis; MTT assay
Description Quaternary benzo[c]phenanthridine alkaloids (QBA) fall into a group of isochinoline alkaloids that have phenylalanin as their precursor. They are isolated from many plant species for instance from Papaveraceae, Fumariaceae and Rutaceae families. Sanguinarin and chelerytrin are the two best known QBA and their biological activities have been widely studied (1,2,3). In addition to them about 10 other QBA differing only by substitution on the aromatic rings have been isolated as a minor components in several species. The informations about biological effects of this minor QBA are rare. In this study the biological effect of sanguinarine (SA), chelerythrine (CHE) and their derinates sanguirubine (SR), chelirubine (CHR) and macarpine (MA) were tested. One normal (skin fibroblasts) and 3 tumour cell lines (HeLa; A 431; HL-60) were used as a model object. Cytotoxicity (IC50) and apoptosis on living cells were studied. After 72 hours, MTT assay was performed to evaluate the in vitro cytotoxicity induced by tested alkaloids at concentration 0,01-5ěg/ml. Promyelocytic leukemia cell line HL-60 has been proved the most sensitive to the alkaloid treatment followed by skin fibroblasts, while the carcinoma cell lines HeLa and A-431 appeared much more resistant. Cytotoxicity of individual alkaloids descended (the value of IC50 increased) in this order CHE > MA > SA > SR > CHR. 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 PI was applied. SA, CHE, MA and SR appeared to be inductors of apoptosis. This work was supported by the grants 525/040017 and 301/03/H005 from the Grant agency of Czech republic and MSM0021622415 from Ministry of Education of the Czech Republic
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