RRC ID 38487
Author Kikuchi T, Ishii K, Noto T, Takahashi A, Tabata K, Suzuki T, Akihisa T.
Title Cytotoxic and apoptosis-inducing activities of limonoids from the seeds of Azadirachta indica (neem).
Journal J. Nat. Prod.
Abstract 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).
Volume 74(4)
Pages 866-70
Published 2011-4-25
DOI 10.1021/np100783k
PMID 21381696
MeSH Antineoplastic Agents, Phytogenic / chemistry Antineoplastic Agents, Phytogenic / isolation & purification* Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects* Azadirachta / chemistry* Drug Screening Assays, Antitumor HL-60 Cells Humans Limonins / chemistry Limonins / isolation & purification* Limonins / pharmacology* Lymphocytes / drug effects Mitochondria / drug effects Molecular Structure Receptors, Death Domain / drug effects Seeds / chemistry
IF 4.257
Times Cited 40
Human and Animal Cells