Inhibitory effects of a new oral gold compound on HeLa cells

Cancer. 1979 Dec;44(6):1965. doi: 10.1002/1097-0142(197912)44:6<1965::aid-cncr2820440602>3.0.co;2-6.

Abstract

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.

MeSH terms

  • Aurothioglucose / analogs & derivatives*
  • Aurothioglucose / pharmacology
  • Cell Division / drug effects
  • Cell Membrane / drug effects
  • Cell Survival / drug effects
  • DNA / biosynthesis
  • Gold / analogs & derivatives*
  • HeLa Cells / drug effects*
  • HeLa Cells / metabolism
  • HeLa Cells / ultrastructure
  • Humans
  • Microscopy, Electron, Scanning
  • Oxygen Consumption / drug effects
  • Phosphines / pharmacology
  • Protein Biosynthesis
  • RNA / biosynthesis

Substances

  • Phosphines
  • Aurothioglucose
  • RNA
  • Gold
  • DNA