title: Cytotoxicity of nimbolide, epoxyazadiradione and other limonoids from neem insecticide.
abstract: Neem seed preparations contain not only azadirachtin as the active insect antifeedant or growth regulator but also a variety of their limonoids, some of which are cytotoxic to N1E-115 neuroblastoma (mouse), 143B.TK- osteosarcoma (human) and Sf9 (insect) cultured cell lines. The most potent of these limonoids is nimbolide with an IC50 ranging from 4 to 10 microM, and averaging 6 microM for the three cell lines. Other limonoids of decreasing potency and their average IC50 values (microM) are epoxyazadiradione 27 microM, salannin 112 microM, and nimbin, deacetylnimbin and azadirachtin each >200 microM (practically nontoxic). Nimbolide at 10 microM acts rapidly in the neuroblastoma cells to induce blebbing associated with disruption of plasma membranes almost instantaneously and 50% loss of cell viability with 30 min. At 5 microM nimbolide, the cells become elongated and assume a neuronal shape accompanied by spikes and lamellipodia within 1-2 hr followed shortly thereafter by extensive cytological changes and and vacuolization associated with irreversible processess leading to cell death. Calcium is apparently not involved the cytotoxic effect since a calcium-free medium, leading to profound morpholigical changes, does not alter the sensitivity to nimbolide. In contrast, epoxyazadiradione requires higher concentrations and a few hr for 50 % viability loss without major morphological changes, indicating a difference in mode of action for nimbolide and epoxyazadiradione. and epoxyazadiradione.
authors.affiliation: Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cohen
authors.forename: G B
authors.initials: GB
authors.lastname: Quistad
authors.forename: J E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D004224:Diterpenes / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007783:Lactones / Q000633:toxicity*; D036701:Limonins; D008297:Male; D051379:Mice; D009447:Neuroblastoma; D009654:Norsteroids / Q000633:toxicity*; D012516:Osteosarcoma; D011817:Rabbits; D012639:Seeds; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects; D018411:Spodoptera; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D003603:Cytotoxins; D004224:Diterpenes; D007306:Insecticides; D007783:Lactones; D036701:Limonins; D009654:Norsteroids; D014315:Triterpenes; C099260:epoxyazadiradione; C042198:nimbolide; C008621:nimbin