| Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG. | |
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MedLine Citation:
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PMID: 20434464 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Palrasu Manikandan; Ramalingam Senthil Murugan; Ramamurthi Vidya Priyadarsini; Govindarajah Vinothini; Siddavaram Nagini |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-29 |
Journal Detail:
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Title: Life sciences Volume: 86 ISSN: 1879-0631 ISO Abbreviation: Life Sci. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-08-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 936-41 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Blotting, Western Densitometry Disease Models, Animal Eugenol / pharmacology* Gene Expression Regulation, Neoplastic / drug effects Immunohistochemistry Male Matrix Metalloproteinase 2 / genetics, metabolism Matrix Metalloproteinase 9 / genetics, metabolism Methylnitronitrosoguanidine* Neoplasm Invasiveness Neoplasm Proteins / genetics, metabolism Neovascularization, Pathologic / drug therapy, genetics, pathology, prevention & control* Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / blood supply*, chemically induced*, genetics, pathology |
| Chemical | |
Reg. No./Substance:
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0/Neoplasm Proteins; 70-25-7/Methylnitronitrosoguanidine; 97-53-0/Eugenol; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
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