Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells |
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Authors: | Slaninová I Táborská E Bochoráková H Slanina J |
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Institution: | (1) Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic;(2) Department of Biochemistry, Faculty of Medicine, Masaryk University, Brno, Czech Republic |
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Abstract: | We compared the effects of four quaternary benzoc]phenanthridine alkaloids – chelerythrine, chelilutine, sanguinarine, and sanguilutine – and two quaternary protoberberine
alkaloids – berberine and coptisine – on the human cell line HeLa (cervix carcinoma cells) and the yeastsSaccharomyces cerevisiae andSchizosaccharomyces japonicus var. versatilis. The ability of alkaloids to display primary fluorescence, allowed us to record their dynamics and localization in cells.
Cytotoxic, anti-microtubular, and anti-actin effects in living cells were studied. In the yeasts, neither microtubules nor
cell growth was seriously affected even at the alkaloid concentration of 100 μg/ml. The HeLa cells, however, responded to
the toxic effect of alkaloids at concentrations ranging from 1 to 50 μg/ml. IC50 values for individual alkaloids were: sanguinarine IC50 = 0.8 μg/ml, sanguilutine IC50 = 8.3 μg/ml, chelerythrine IC50 = 6.2 μg/ml, chelilutine IC50 = 5.2 μg/ml, coptisine IC50 = 2.6 μg/ml and berberine IC50 >10.0 μg/ml. In living cells, sanguinarine produced a decrease in microtubule numbers, particularly at the cell periphery,
at a concentration of 0.1 μg/ml. The other alkaloids showed a similar effect but at higher concentrations (5–50 μg/ml). The
strongest effects of sanguinarine were explained as a consequence of its easy penetration through the cell membrane owing
to nonpolar pseudobase formation and to a high degree of molecular planarity.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | benzo[c]phenanthridine alkaloids cytoskeleton cytotoxicity HeLa cells protoberberine alkaloids yeasts |
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