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Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG.

Authors: Manikandan, P  Murugan, RS  Priyadarsini, RV  Vinothini, G  Nagini, S 
Citation: Manikandan P, etal., Life Sci. 2010 Apr 29.
Pubmed: (View Article at PubMed) PMID:20434464
DOI: Full-text: DOI:10.1016/j.lfs.2010.04.010

AIMS: Combining apoptosis induction with anti-invasive and anti-angiogenic treatment is gaining increasing attention as a promising strategy for cancer chemoprevention. In the present study, eugenol (4-allyl-2-methoxyphenol) was evaluated for its chemopreventive effects on N-methyl-N(')-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats by analyzing markers of apoptosis, invasion and angiogenesis. MAIN METHODS: The expressions of markers of apoptosis (Bcl-2, Bcl-xL, Bax, Apaf-1, cytochrome C, caspase-9, caspase-3 and poly(ADP-ribose)polymerase; PARP), invasion (matrix metalloproteinase-2; MMP-2, matrix metalloproteinase-9; MMP-9, reversion-inducing cysteine rich protein with Kazal motifs; RECK and tissue inhibitors of metalloproteinase-2; TIMP-2) and angiogenesis (vascular endothelial growth factor; VEGF and VEGF receptor1; VEGFR1) in stomach tissue of experimental and control animals were measured by gelatin zymogram, immunohistochemical, Western blot and RT-PCR analysis. KEY FINDINGS: Rats administered MNNG developed gastric carcinomas that displayed apoptosis avoidance coupled to upregulation of pro-invasive and angiogenic factors. Administration of eugenol induced apoptosis via the mitochondrial pathway by modulating the Bcl-2 family proteins, Apaf-1, cytochrome C, and caspases and inhibiting invasion, and angiogenesis as evidenced by changes in the activities of MMPs and the expression of MMP-2 and -9, VEGF, VEGFR1, TIMP-2 and RECK. SIGNIFICANCE: Phytochemicals such as eugenol that are capable of manipulating the equilibrium between pro- and anti-apoptotic proteins as well as the delicate balance between stimulators and inhibitors of invasion and angiogenesis are attractive candidates for preventing tumour progression.


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CRRD Object Information
CRRD ID: 2325777
Created: 2010-06-09
Species: All species
Last Modified: 2010-06-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.