Cytotoxic and genotoxic effects of cleistanthin B in normal and tumour cells

Cleistanthin B, one of the toxic constituents of Cleistanthus collinus, was found to be cytotoxic to normal and tumour cells. In comparison with normal cells, tumour cells were sensitive to lower doses of toxin. The 50% growth inhibition (GI50) values for normal cell lines were from 2 x 10(-5) to 4.7 x 10(-4) M and for tumour cells the values ranged from 1.6 x 10(-6) to 4 x 10(-5) M. Short exposure (30 min) of Chinese hamster ovary (CHO) cells to cleistanthin B at 1-6 micrograms/ml resulted in extensive chromatid and isochromatid breaks and gaps. However there was no significant increase in cell death and DNA strand breaks in cells treated under the above conditions. Cleistanthin B induced micronucleus formation in cultured lymphocytes in a dose-dependent manner. CHO cells treated with high doses of cleistanthin B showed a decrease in cell viability and a concomitant increase in DNA strand-breaks. The cell death appears to be due to apoptosis since nucleosome-like ladders were observed in the treated cells when the DNA was electrophorized in agarose gels.