Biological effects of benzo[c]phenanthridine alkaloids.

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Authors

SLUNSKÁ Zdenka SLANINOVÁ Iva SINKORA Jiri VLKOVA Marcela TÁBORSKÁ Eva

Year of publication 2005
Type Article in Proceedings
Conference Journal of Applied Biomedicine
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords benzo[c]phenanthridine alkaloids; apoptosis; cytotoxicity; MTT assay
Description Quaternary benzo[c]phenanthridine alkaloids (QBA) are group of natural products, which are discussed as potencial cytostatics for cancer treatment. QBA are relatively small group of isoquinoline alkaloids that have phenylalanin as their precursor. They are distributed in a number of plant species of Papaveraceae, Fumariaceae and Rutaceae families. Sanguinarin and chelerythrin 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. The informations about biological effects of this minor QBA are rare. In this study the differential cytotoxicity of sanguinarine (SA), chelerythrine (CHE) and their minority derivates sanguirubine (SR), chelirubine (CHR) and macarpine (MA) was assessed in vitro by MTT assay. One normal (skin fibroblasts) and 3 tumour cell lines (HeLa; A 431; HL-60) were used as a model object. After 72 hours, MTT assay was performed to evaluate the in vitro cytotoxicity induced by tested alkaloids. Our results show that HL-60 and skin fibroblasts were the most sensitive cell culture lines, while the carcinoma cell lines HeLa and A-431 appeared much more 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 PI was applied. All tested alkaloids appeared to be inductors of apoptosis. Based on our observations we concluded that alkaloids tested in this study show strong antiproliferative and proapoptotic effect in vitro. 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 References: 1) Walterová, D., Ulrychová, J., Válka, I., et al., Acta Univ. Palacki Olomouc Fac. Med. 1995; 139:7-14. 2) Šimánek, V., Vespalec, R., Šedo,A., Ulrichová, J., Vičar, J. 2003. Quaternary Benzo(c)phenanthridine alkaloids - biological activities. In: M.P.Schneider (Ed.), Chemical Probes in Biology. Kluwer Academic Publishers, Netherlands. pp 245-254. 3) Slaninová,I., E.Taborská, H.Bochořáková, and J.Slanina. 2001. Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells. Cell Biology and Toxicology 17:51-63.
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