Journal
PHARMACEUTICAL BIOLOGY
Volume 45, Issue 2, Pages 131-139Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880200601113099
Keywords
annexin V; apoptosis; benzo(c)phenanthridine alkaloids; chelerythrine; chelirubine; cytotoxicity; macarpine; MTT assay; sanguinarine; sanguirubine
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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, chelirubirie, and macarpine and better known benzophenanthridines sanguinarine and chelerythrine in cancer and normal cells wag assessed in vitro by MTT assay using a panel consisting of either transformed cell lines (HeLa; A431; HL60) of primary fibroblasts of human origin; IC50 values were determined 12 h after addition of the alkaloids. A wide range (0.01-1.44 mu g/mL) Of IC50 was observed, and the highest toxicity was determined for macarpine. Human promyelocytic leukemia line HL60 has been documented to be 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 was selected for demonstrating the ability of the alkaloids to induce apoptosis by analyzing morphologic changes upon DAPI staining, ultrastructural changes, and annexin V versus propidium iodide staining assay. Apoptosis was induced by sanguirubine, chelirubine, chelerythrine, and macarpine at a concentration of I mu g/mL. The results show that the alkaloids tested have a strong antiproliferative effect in vitro due predominately to apoptosis.
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