Inhibitory effects of a new oral gold compound on HeLa cells.
Auranofin (AF), a recently introduced oral antirheumatic coordinated gold compound, was investigated for its antitumor potential. Due to certain similarities with the antitumor-coordinated compound, cis-Diamminedichloroplatinum II, we studied the effects of AF on cell proliferation. These studies included assessing DNA, RNA, and protein synthesis as measured by incorporation of 3H-thymidine, 3H-uridine, and 3H-leucine, respectively, into HeLa cells. AF was shown to exert a dose-dependent inhibition on DNA synthesis and to inhibit 3H-thymidine uptake more rapidly and persistently than 3H-uridine or 3H-leucine uptake at a gold concentration of 75--100 micrograms/dl. These three parameters were inhibited with a 24-hour exposure to 100 micrograms/dl. The inhibition of 3H-thymidine uptake in HeLa pretreated for 6 hours with 50 or 100 micrograms/dl of gold was found to be irreversible. No change in tracer uptake was observed in the acid-soluble pool or in the uptake of 3H-2-deoxy-D-glucose in these cells. Furthermore, HeLa cells demonstrated marked reductions in viability and oxygen uptake after exposure to AF. Dose-dependent surface morphological changes, e.g., blebbing, pitting, were noted in these cells after a brief treatment period. These results suggest this coordinated gold compount exerts a significant inhibitory effect on essential biological processes and functions.
D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006046:Gold / Q000031:analogs & derivatives*; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010101:Oxygen Consumption / Q000187:drug effects; D010720:Phosphines / Q000494:pharmacology; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis
D010720:Phosphines; D006051:Aurothioglucose; D012313:RNA; D006046:Gold; D004247:DNA