The role of polyamines in interferon and retinoic acid mediated synergistic antiproliferative action.
Retinoic acid alone has no effect on the human breast cancer cell line BT-20 but can amplify the antiproliferative action of interferon-gamma (IFN-gamma). In our system ornithine decarboxylase (ODC) activity correlates well with growth rate; it was investigated whether the antiproliferative effects of IFN-gamma and IFN-gamma plus retinoic acid could be attributed to suppression of ODC activity. The ODC inhibitor difluoromethylornithine (DFMO), which is active as a single agent did not enhance growth inhibition induced by the biological response modifiers. The substitution of the BT-20 cells with putrescine, the product of the enzymatic reaction mediated by ODC, reversed DFMO induced antiproliferative action. On the other hand putrescine did not affect the proliferation of BT-20 cells treated with interferon alone or in combination with retinoic acid.
Marth
C
C
Department of Obstetrics and Gynecology, University Hospital, Innsbruck, Austria.
Kirchebner
P
P
Daxenbichler
G
G
D015317:Biogenic Polyamines / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D065108:Ornithine Decarboxylase Inhibitors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; D065108:Ornithine Decarboxylase Inhibitors; D014212:Tretinoin; D007371:Interferon-gamma; D000518:Eflornithine