Antitumor Effect of Gold as Revealed by Growth Suppression of Cultured Cancer Cells

Abstract

Gold agents have been widely used for the treatment of rheumatoid arthritis. We studied the growth inhibiting effect of such an agent on malignant cells in vitro.

HCT-15, AGS cells derived from a human malignancy, and Meth/A cells from a malignant lymphoma of Balb/C mice were cultured separately with gold agent at concentrations of 2 μg/ml. Four days after the cultures had been incubated in a 5% C0₂ incubator at 37°C, cell counts were made; and significance of differences was analyzed by Student's t test. Additionally, HCT-15 cells were cultured with gold for two days, and then the cells were analyzed by flow cytometry.

The growth of HCT-15, AGS, and Meth/A cells was suppressed by gold. Fifty percent suppression was observed at a concentration between 50 μg/ml and 10 μg/ml for HCT-15 cells, between 125 μg/ml and 50 μg/ml for AGS cells, and between 125 μg/ml and 50 μg/ml for Meth/A cells. Fifty percent suppression of HCT-15 cell growth by cisplatinum was found between 50 μg/ml and 10 μg/ml.

Flow cytometric findings showed a significant rise in the tetraploid peak, a mild rise in the resion between diploid and tetraploid peaks, and an increase in cells with a ploidy greater than four. These data suggest that gold blocks the S phase, G2 to M phase, and M phase as well.

To observe the cytotoxicity of gold, each of 10 of 4 week-old Balb/C mice was injected s.c. at a dose of 10 mg/kg or 2 mg/kg every other day for a total of 3 injections, or was administered the gold at 30 mg/kg/day p.o. for 10 days. All mice were still alive after 20 days of observation. Cisplatinum at a dose of 10 mg/kg was also injected s.c. one time into each of 10 mice, and 60% of the animals died within 10 days after the injection.