Growth inhibition and induction of phenotypic alterations by tiazofurin: Differential effects on MCF-7 breast cancer and HBL-100 breast cell lines

Abstract

The effect of the nucleoside anti-metabolite tiazofurin (TR) was examined on the growth and phenotypic alterations of MCF- 7 breast cancer and HBL- 100 normal breast cell lines. TR was shown to inhibit MCF- 7 cell growth. This inhibition could be reversed by exogenous addition of guanosine. The anti-proliferative effect of TR is accompanied by phenotypic alterations that include lipid accumulation and an increase in alkaline phosphatase activity. In contrast to MCF- 7 cells, the HBL- 100 breast milk derived cell line is relatively resistant to inhibition by TR. Alkaline phosphatase is not affected by TR and untreated cells accumulate lipid droplets, similar to TR-treated MCF- 7 cells. Determination of GTP and ATP pools in both cell lines revealed that TR markedly reduces GTP content in MCF- 7 cells. In HBL- 100 cells, TR induces only a small decrease in GTP and does not affect ATP levels. The prototypic IMP dehydrogenase inhibitor, mycophenolic acid (MA), markedly inhibits HBL- 100 cell growth, similarly to its effect on MCF- 7 breast cancer cells. These findings may suggest differential metabolism of TR in MCF- 7 and HBL- 100 cells.