HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cytotoxic and apoptosis-inducing activities of limonoids from the seeds of Azadirachta indica (neem).

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).
AuthorsTakashi Kikuchi, Koichi Ishii, Taisuke Noto, Akitomo Takahashi, Keiichi Tabata, Takashi Suzuki, Toshihiro Akihisa
JournalJournal of natural products (J Nat Prod) Vol. 74 Issue 4 Pg. 866-70 (Apr 25 2011) ISSN: 1520-6025 [Electronic] United States
PMID21381696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Limonins
  • Receptors, Death Domain
  • azadiradione
  • 28-deoxonimbolide
  • gedunin
  • nimbin
  • azadirachtin
Topics
  • Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
  • Apoptosis (drug effects)
  • Azadirachta (chemistry)
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans
  • Limonins (chemistry, isolation & purification, pharmacology)
  • Lymphocytes (drug effects)
  • Mitochondria (drug effects)
  • Molecular Structure
  • Receptors, Death Domain (drug effects)
  • Seeds (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: