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The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells
Published in
2010
PMID: 20429769
Volume: 44
   
Issue: 6
Pages: 624 - 634
Abstract
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-κB 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. © 2010 Informa UK Ltd.
About the journal
JournalFree Radical Research
ISSN10715762
Open AccessNo
Concepts (53)
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    Azadirachtin
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    CASPASE
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    CYCLIN B
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    Cyclin d1
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    CYCLINE
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    Cytochrome c
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    Immunoglobulin enhancer binding protein
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    Limonoid
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    NIMBOLIDE
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    Protein bcl 2
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    Protein p21
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    Protein p53
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    SURVIVIN
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    Apoptosis
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    Article
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    Cell cycle arrest
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    Cell cycle g0 phase
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    Cell cycle g1 phase
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    CELL CYCLE REGULATION
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    Cell nucleus
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    Cell viability
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    Concentration response
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    Controlled study
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    Down regulation
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    Drug cytotoxicity
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    Drug effect
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    Drug mechanism
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    Drug synthesis
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    Enzyme release
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    Hela cell
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    Human
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    Human cell
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    Mitochondrial membrane potential
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    Mitochondrion
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    Phenotype
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    Protein expression
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    Protein family
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    Transcription initiation
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    Antioxidants
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    Azadirachta
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    Blotting, western
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    Cell cycle
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    Cell survival
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    Gene expression
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    Hela cells
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    Humans
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    Limonins
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    Membrane potential, mitochondrial
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    Microscopy, fluorescence
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    Mitochondria
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    Polymerase chain reaction
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    Reactive oxygen species
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    Azadirachta indica