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Cytotoxic and Apoptosis-Inducing Activities of Limonoids from the Seeds of Azadirachta indica (Neem).
MedLine Citation:
PMID:  21381696     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Thirty-five limonoids, including 15 of the azadiradione type (1-15), five of the gedunin type (16-20), four of the azadirachtin type (21-24), nine of the nimbin type (25-33), and two degraded limonoids (34, 35), isolated from Azadirachta indica seed extracts, were evaluated for their cytotoxic activities against five human cancer cell lines. Seven compounds (3, 6, 7, 16, 18, 28, and 29) exhibited cytotoxic activity against one or more cell lines. Among these compounds, 7-deacetyl-7-benzoylepoxyazadiradione (7), 7-deacetyl-7-benzoylgeduin (18), and 28-deoxonimbolide (28) exhibited potent cytotoxic activity against HL60 leukemia cells with IC(50) values in the range 2.7-3.1 μM. Compounds 7, 18, and 28 induced early apoptosis in HL60 cells, observed by flow cytometry. Western blot analysis showed that compounds 7, 18, and 28 activated caspases-3, -8, and -9 in HL60 cells. This suggested that compounds 7, 18, and 28 induced apoptotic cell death in HL60 cells via both the mitochondrial- and the death receptor-mediated pathways. Futhermore, compound 7 was shown to possess high selective cytotoxicity for leukemia cells since it exhibited only weak cytotoxicity against a normal lymphocyte cell line (RPMI 1788).
Authors:
Takashi Kikuchi; Koichi Ishii; Taisuke Noto; Akitomo Takahashi; Keiichi Tabata; Takashi Suzuki; Toshihiro Akihisa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-7
Journal Detail:
Title:  Journal of natural products     Volume:  -     ISSN:  1520-6025     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906882     Medline TA:  J Nat Prod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan.
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