Comparison of the antiproliferative properties of antiestrogenic drugs (nafoxidine and clomiphene) on glioma cells in vitro.
The antitumoral activity of nonsteroidal antiestrogens on C6 and low passage of human glioma cells was investigated. Tamoxifen and its metabolite, 4-hydroxytamoxifen, did not influence viability of the human cells, but tamoxifen had a limited antiproliferative effect on C6 cells (IC50: 49 micromol/l). The derivatives of tamoxifen, nafoxidine and clomiphene, caused reduction of living cell number in a dose-dependent manner. These two drugs showed differences in their potency following 24-hour incubation in a humidified atmosphere with 37 degrees C and 5% CO2. Obtained from a tetrazolium-formazan growth rate assay, IC50 of nafoxidine for C6 cells was calculated as 44 micromol/l and for the human cells as 16.5 micromol/l. The calculated IC50 dose of clomiphene for C6 is 16 micromol/l and for the human cells 13 micromol/l. Compared to the other drugs we used, it is clear that clomiphene is the most efficient inhibitor of C6 and the human glioma cells. These preliminary results suggest that nafoxidine and clomiphene possess antiproliferative effect on two different sources of glioma cells and therefore, instead of tamoxifen, multiple activities of these drugs may enable their use in combination therapy of glioblastoma malignancies.
Osmangazi University, Medical Faculty, Department of Physiology, Eskişehir, Turkey.
Gökçen
G
Yaz
Selda
S
Kabadere
Pnar
P
Oztopçu
Ramazan
R
Durmaz
Ruhi
R
Uyar
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002996:Clomiphene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D009256:Nafoxidine / Q000494:pharmacology*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D013629:Tamoxifen; D002996:Clomiphene; D009256:Nafoxidine