Document Detail

The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells.
MedLine Citation:
PMID:  20429769     Owner:  NLM     Status:  MEDLINE    
Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention in recent years owing to their potent antioxidant and anti-proliferative effects. The present study was designed to investigate the cellular and molecular mechanisms by which azadirachtin and nimbolide exert cytotoxic effects in the human cervical cancer (HeLa) cell line. Both azadirachtin and nimbolide significantly suppressed the viability of HeLa cells in a dose-dependent manner by inducing cell cycle arrest at G0/G1 phase accompanied by p53-dependent p21 accumulation and down-regulation of the cell cycle regulatory proteins cyclin B, cyclin D1 and PCNA. Characteristic changes in nuclear morphology, presence of a subdiploid peak and annexin-V staining pointed to apoptosis as the mode of cell death. Increased generation of reactive oxygen species with decline in the mitochondrial transmembrane potential and release of cytochrome c confirmed that the neem limonoids transduced the apoptotic signal via the mitochondrial pathway. Altered expression of the Bcl-2 family of proteins, inhibition of NF-kappaB activation and over-expression of caspases and survivin provide compelling evidence that azadirachtin and nimbolide induce a shift of balance toward a pro-apoptotic phenotype. Antioxidants such as azadirachtin and nimbolide that can simultaneously arrest the cell cycle and target multiple molecules involved in mitochondrial apoptosis offer immense potential as anti-cancer therapeutic drugs.
R Vidya Priyadarsini; R Senthil Murugan; P Sripriya; D Karunagaran; S Nagini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  44     ISSN:  1029-2470     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-10     Completed Date:  2010-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  624-34     Citation Subset:  IM    
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
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MeSH Terms
Antioxidants / pharmacology*
Apoptosis / drug effects*
Azadirachta / chemistry
Blotting, Western
Cell Cycle / drug effects*
Cell Survival / drug effects
Gene Expression / drug effects
Hela Cells
Limonins / pharmacology*
Membrane Potential, Mitochondrial / drug effects
Microscopy, Fluorescence
Mitochondria / drug effects*,  pathology
Polymerase Chain Reaction
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Antioxidants; 0/Limonins; 0/Reactive Oxygen Species; 11141-17-6/azadirachtin; 25990-37-8/nimbolide

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