Effect of gossypol on DNA synthesis and cell cycle progression of mammalian cells in vitro.
Gossypol, a yellow phenolic compound extracted from cotton plants that is being used as a male antifertility drug, has been found to have cytotoxic effects. The objective of the present study was to determine the cause of these cytotoxic effects in cultured cells and to ascertain whether cells in certain phases of the cell cycle were more sensitive to the drug than were cells in other phases. HeLa or Chinese hamster ovary cells were exposed to various concentrations of gossypol for varying periods of time, and the effects of the drug on the growth rate, cell cycle traverse, plating efficiency, and macromolecular synthesis were measured. The results of this study indicate that gossypol is a specific inhibitor of DNA synthesis; it has no effect on RNA and protein synthesis at a concentration of 10 micrograms/ml and hence has no effect on the cell cycle traverse of cells from G2 to the beginning of S phase. In the presence of the drug, cells can enter S phase but fail to complete replication. The effects of the drug on growth rate and plating efficiency indicate that there is a threshold concentration at which gossypol becomes effective as a cytotoxic agent. Gossypol did not increase chromosome aberrations in the treated cells. Since gossypol irreversibly blocks cells in S phase, it could be useful as an antitumor drug.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002459:Cell Fusion; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D006072:Gossypol / Q000633:toxicity*; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D010053:Ovary
D006072:Gossypol