Antiproliferative properties of the lazaroids U-83836E and U-74389G on glioma cells in vitro.
The 21-aminosteroids (lazaroids) are a new family of steroid compounds that inhibit lipid peroxidation reactions. They are novel antioxidant agents, which have been shown to have antiproliferative properties on cancer cells and also are thought to prevent free radical-mediated blood-brain barrier damage. In order to understand the effect of lazaroids on glioma, we tested U-83836E and U-74389G at doses ranging between 0.1 100 m mM on primary cultures of glioblastoma multiforme from three patients, rat C6 glioma cell line, and 5 th subculture established from one of the patients. The effects of both compounds on cell proliferation were determined using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay. U-83836E in the primary cultures was found to have 50% inhibitory concentrations (IC50 ) of 6.30, 6.75 and 6.50 m mM, respectively. The IC50 value of U-74389G was calculated as 91 m mM in only one of the patients. On C6 glioma cells, while the IC50 of U-83836E was 45 m mM, U-74389G showed no cytotoxic effect. On the 5 th subculture, U-83836E had an IC50 of 37.5 m mM, but the cytotoxic effects of U-74389G was less than in that of the primary culture. In conclusion, these compounds were found to be more cytotoxic in primary culture than the cell lines and there were also differences between their members in the inhibition of cell survival.
Durmaz
R
R
Medical Faculty of Osmangazi University, Department of Neurosurgery, Eskisehir, 90-26480, Turkey. rdurmaz@ogu.edu.tr
Deliorman
S
S
Isiksoy
S
S
Uyar
R
R
Erol
K
K
Tel
E
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000473:pathology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D002839:Chromans; D010879:Piperazines; D011281:Pregnatrienes; C074965:U 74389F; C066382:U 78517F