Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells

We compared the effects of four quaternary benzo[c]phenanthridine alkaloids - chelerythrine, chelilutine, sanguinarine, and sanguilutine - and two qua ternary protoberberine alkaloids - berberine and coptisine - on the human c ell line HeLa (cervix carcinoma cells) and the yeasts Saccharomyces cerevis iae and Schizosaccharomyces japonicus var. versatilis. The ability of alkal oids to display primary fluorescence, allowed us to record their dynamics a nd localization in cells. Cytotoxic, anti-microtubular, and anti-actin effe cts in living cells were studied. In the yeasts, neither microtubules nor c ell growth was seriously affected even at the alkaloid concentration of 100 mug/ml. The HeLa cells, however, responded to the toxic effect of alkaloid s at concentrations ranging from 1 to 50 mug/ml. IC50 values for individual alkaloids were: sanguinarine IC50 = 0.8 mug/ml, sanguilutine IC50 = 8.3 mu g/ml, chelerythrine IC50 = 6.2 mug/ml, chelilutine IC50 = 5.2 mug/ml, copti sine IC50 = 2.6 mug/ml and berberine IC50 > 10.0 mug/ml. In living cells, s anguinarine produced a decrease in microtubule numbers, particularly at the cell periphery, at a concentration of 0.1 mug/ml. The other alkaloids show ed a similar effect but at higher concentrations (5-50 mug/ml). The stronge st effects of sanguinarine were explained as a consequence of its easy pene tration through the cell membrane owing to nonpolar pseudobase formation an d to a high degree of molecular planarity.