Cytotoxicity of azadirachtin A in human glioblastoma cell lines

The neem toxin azadirachtin A exhibits selective toxicity on insects. Despi te its well-proven efficacy, the mode of action of this toxin remains obscu re. The toxicity on vertebrate cells compared to insect cells is also not w ell characterized. We have cultivated six human glioblastoma cell lines G-2 8, G-112, G-60 (TP53 mutant) and G-44, G-62, G-120 (TP53 wild-type) in the presence of 28 muM of azadirachtin. This toxin concentration was chosen bec ause it represents the 25 to 50% lethal dose in the glioma cells. Toxicity was measured in terms of cell proliferation (binucleation index), formation of micronuclei and cell survival. In the TP53 mutant cell lines, azadirach tin reduced the proportion of dividing cells and induced formation of micro nuclei. Except for G-44 which showed a decrease in binucleation index, prol iferation in the TP53 wild-type cell lines was unaffected by azadirachtin. In the TP53 wild-type cell lines, the decrease in micronuclei frequency is attributed to fewer cells entering mitosis to produce micronuclei. This is also apparent from the low surviving fractions. Cell survival was suppresse d by 25-69% in all cell lines. The reduction of cell survival is a clear in dication that azadirachtin affects reproductive integrity and cell division . The induction of micronuclei reflects DNA damage. Similar studies on dama ge induction in insect cell lines could elucidate the processes which prece de the antifeedant and antimoulting effects of azadirachtin and other neem toxins in insects. (C) 2001 Elsevier Science Inc. All rights reserved.