Growth inhibition and induction of phenotypic alterations in MCF-7 breast cancer cells by an IMP dehydrogenase inhibitor.

Y Sidi, C Panet, L Wasserman, A Cyjon… - British journal of …, 1988 - ncbi.nlm.nih.gov
Y Sidi, C Panet, L Wasserman, A Cyjon, A Novogrodsky, J Nordenberg
British journal of cancer, 1988ncbi.nlm.nih.gov
Guanine ribonucleotides (GuRN) play a major role in multiple cellular functions related to
cell proliferation including DNA, RNA and protein synthesis (Weber, 1983). Intracellular
GuRN concentration is mainly determined by the activity of inosinate (IMP) dehydrogenase
and the availability of guanine for salvage by hypoxanthine guanine phosphoribosyl
transferase (HGPRT). The activity of IMP dehydrogenase was shown to be markedly
increased in transformed cells (Weber, 1977). Inhibitors of IMP dehydro-genase were found …
Guanine ribonucleotides (GuRN) play a major role in multiple cellular functions related to cell proliferation including DNA, RNA and protein synthesis (Weber, 1983). Intracellular GuRN concentration is mainly determined by the activity of inosinate (IMP) dehydrogenase and the availability of guanine for salvage by hypoxanthine guanine phosphoribosyl transferase (HGPRT). The activity of IMP dehydrogenase was shown to be markedly increased in transformed cells (Weber, 1977). Inhibitors of IMP dehydro-genase were found to be cytotoxic towards several tumour lines including those unresponsive to other chemotherapeutic agents (Sweeney et al., 1972; Carney et al., 1985; Connoly & Halsall, 1975). IMP dehydrogenase inhibitors have recently been shown to induce cell differentiation in the promyelocytic cell line HL-60 (Lucas et al., 1983; Wright, 1987). In the present study we examined the effects of myco-phenolic acid (MA) on breast cancer cell lines. MA represents a prototypic IMP dehydrogenase inhibitor, with no other biochemical effects noted (Franklin & Cook, 1969; Lee et al., 1985). Most studies were performed on the MCF-7 breast cancer cell line and selected experiments were done with the T-47D cell line. Cells were cultured as previously described (Wasserman et al., 1987). For growth experiment cells (105ml-1) were plated in culture medium (1.5 ml-RPMI 1640 supplemented with 10% foetal calf serum and antibiotics) in the absence and presence of MA. Seventy-two hours later the cells were detached with EDTA (1 mM) and counted in a Coulter counter.
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