Lipoxygenase inhibitors suppress proliferation of G5:113 fibrosarcoma cells in vitro but they have no anticancer activity in vivo.
Nordihydroguaiaretic acid (NDGA) and esculetin, both nonspecific inhibitors of lipoxygenases (LOX), were found to suppress expressively the in vitro proliferation of fibrosarcoma cells G5:113 in concentrations ranging from 10 to 50 microM. Subsequent flow-cytometric analysis of the cell cycle showed that both these drugs significantly decreased the percentage proportion of cells in the G0/G1-phase and simultaneously increased significantly this proportion in the S-phase. No apoptosis was detected in the whole range of concentrations studied, from 2.5 to 50 mM. On the contrary, in experiments in vivo, neither NDGA nor esculetin had any curative effect if they were repeatedly injected intraperitoneally (i.p.) into mice bearing tumors growing from subcutaneously (s.c.) transplanted G5:113 cells. Pretreatment of the fibrosarcoma cells with NDGA or esculetin in vitro preceding their s.c. transplantation into mice did not result in suppression of the tumor growth, either. Finally, if G5:113 cells were injected intravenously and the mice were subsequently treated repeatedly with i.p. injections of NDGA, decreased survival and increased number of surface lung metastases were observed in the NDGA-treated group. Thus the suppressive action of inhibitors of LOX on the growth of fibrosarcoma cells in vitro was not reflected in their anti-tumor effects in vivo.
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic. zhofer@ibp.cz
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Z
Hoferová
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Fedorocko
M
M
Hofer
J
J
Hofmanová
A
A
Kozubík
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V
Eliásová
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D014407:Tumor Cells, Cultured; D014468:Umbelliferones / Q000494:pharmacology
D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; D014468:Umbelliferones; D009637:Masoprocol; C007628:esculetin