Screening of minor benzo(c)phenanthridine alkaloids for antiproliferative and apoptotic activities.
|Year of publication||2007|
|Type||Article in Periodical|
|Magazine / Source||Pharmaceutical Biology|
|MU Faculty or unit|
|Field||Genetics and molecular biology|
|Keywords||apoptosis; annexin V; benzo[c]phenanthridine alkaloids; cytotoxicity; chelerythrine; chelirubine; macarpine; MTT assay; sanguinarine; sanguirubine|
|Description||Quaternary benzo[c]phenanthridine alkaloids are a relatively small group of isoquinoline alkaloids with attractive biological activities. They are produced by a number of plant species of the Papaveraceae, Fumariaceae and Rutaceae families. Differential cytotoxicity of minor naturally occurring derivatives sanguirubine, chelirubine and macarpine and better known benzophenanthridines sanguinarine and chelerythrine in cancer and normal cells was assessed in vitro by MTT assay using a panel consisting of either transformed cell lines (HeLa; A431; HL60) or primary fibroblasts of human origin. IC50 values were determined 72 h after addition of the alkaloids. A wide range (0.01-1.44 mg/ml) of IC50 was observed and the highest toxicity was determined for macarpine. Human promyelocytic leukemia line HL60 has been documented the most sensitive to alkaloid treatment followed by human skin fibroblasts, while human cervix adenocarcinoma HeLa cells and epidermal carcinoma cells A431 appeared more resistant. The most sensitive cell line HL60 were selected for demonstrating the ability of the alkaloids to induce apoptosis by analysing morphological changes upon DAPI staining, ultrastructural changes and annexin V versus propidium iodide staining assay. The apoptosis was induced by sanguirubine, chelirubine, chelerythrine and macarpine at the concentration of 1 mg/ml. The results show that the alkaloids tested have strong antiproliferative effect in vitro due predominantly to apoptosis.|