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

Abstract

An ideal anticancer drug would be one that preferentially kills tumor cells with the least toxicity to normal cells. Cleistanthin A, a diphyllin glycoside of the tropical plant Cleistanthus collinus, was found to possess cytotoxic and tumor regressing properties. To find out whether this compound acts selectively on proliferating cells it was tested against quiescent and proliferating human lymphocytes. Mitogen-stimulated and unstimulated human lymphocytes 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 and unstimulated cells and percentage viability of stimulated and treated cells were normalized to that of stimulated and untreated cells. Quiescent lymphocytes were refractory to the action of cleistanthin A. Only proliferating cells were killed. Cell death was proportional to the percentage of cells in the proliferating stage and was also dose-dependent. Quiescent lymphocytes pretreated with cleistanthin A had the ability to proliferate upon subsequent stimulation with PHA. These results indicate that cleistanthin A does not affect the viability of quiescent cells. Also, it did not affect the proliferating potential of quiescent cells. However, this compound drastically affected proliferating cells by reducing their viability to 10-20%. Our results therefore indicate that the antiproliferative property of cleistanthin A could be used in regimens for treating tumors with extensive proliferative potencies.