Cleistanthin A, a diphyllin glycoside from Cleistanthus collinus, is cytotoxic to PHA-Stimulated (Proliferating) human lymphocytes

An ideal anticancer drug would be one that preferentially kills tumor cells with the least toxicity to normal cells. Cleistanthin A, a diphyllin glyco side of the tropical plant Cleistanthus collinus, was found to possess cyto toxic and tumor regressing properties. To find out whether this compound ac ts selectively on proliferating cells it was tested against quiescent and p roliferating human lymphocytes. Mitogen-stimulated and unstimulated human l ymphocytes were treated with cleistanthin A. A cytotoxicity assay using MTT was used to assess the viability of the cells. Percentage viability of the unstimulated and treated cells were normalized to that of the untreated an d unstimulated cells and percentage viability of stimulated and treated cel ls were normalized to that of stimulated and untreated cells. Quiescent lym phocytes were refractory to the action of cleistanthin A. Only proliferatin g cells were killed. Cell death was proportional to the percentage of cells in the proliferating stage and was also dose-dependent. Quiescent lymphocy tes pretreated with cleistanthin A had the ability to proliferate upon subs equent stimulation with PHA. These results indicate that cleistanthin A doe s not affect the viability of quiescent cells. Also, it did not affect the proliferating potential of quiescent cells. However, this compound drastica lly affected proliferating cells by reducing their viability to 10-20%. Our results therefore indicate that the antiproliferative property of cleistan thin A could be used in regimens for treating tumors with extensive prolife rative potencies. Drug Dev. Res. 51:187-190, 2000. (C) 2001 Wiley-Liss, Inc .