Growth inhibition and induction of phenotypic alterations by tiazofurin: differential effects on MCF-7 breast cancer and HBL-100 breast cell lines.
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.
Sidi
Y
Y
Rogoff Medical Research Institute, Department of Medicine D, Beilinson Medica Center, Petah Tikva, Israel.
Beery
E
E
Panet
C
C
Wasserman
L
L
Novogrodsky
A
A
Nordenberg
J
J
D000255:Adenosine Triphosphate / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000032:analysis / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006160:Guanosine Triphosphate / Q000032:analysis; D006801:Humans; D008895:Milk, Human / Q000166:cytology*; D009173:Mycophenolic Acid / Q000494:pharmacology; D012254:Ribavirin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D012263:Ribonucleosides / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000187:drug effects / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D012263:Ribonucleosides; D012254:Ribavirin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D009173:Mycophenolic Acid; C033706:tiazofurin