Antiproliferative action of neomycin is associated with inhibition of cyclin D1 activation in glioma cells.
The progression of mammalian cells through G1 phase of the cell cycle is governed by the D-type cyclins (D1, D2, D3). These proteins are induced at the beginning of the G1 phase and associate with serine/threonine cyclin-dependent kinases to form holoenzymes. Overexpression of cyclin D1 in human cancers as well as in several cancer cell lines has been reported. Here, we employed mitotic selection to synchronize the C6 glioma cell cycle at the start of the G1 phase and assessed the effects of neomycin on cyclin D1 protein detection by immunocytochemical analysis. Cyclin D1 activation as well as cell proliferation were already significantly reduced after 3 h of incubation of the cells with neomycin. These findings suggested that the antiproliferative effects of neomycin in gliomas could be mediated by inhibition of the expression of cyclin D1 gene and support further consideration of therapeutic use of neomycin in a Phase I clinical study for patients with recurrent glioblastoma.
Departmento de Investigación, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Ctra. de Colmenar, km. 9.100, E-28034-Madrid, Spain. pedro.cuevas@hrc.es
Pedro
P
Cuevas
Diana
D
Díaz-González
Manuel
M
Dujovny
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000502:physiology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology*; D051381:Rats
D019938:Cyclin D1; D009355:Neomycin