Ellagic acid normalizes mitochondrial outer membrane permeabilization and attenuates inflammation-mediated cell proliferation in experimental liver cancer.

Srigopalram, S; Jayraaj, I A; Kaleeswaran, B; Balamurugan, K; Ranjithkumar, M; Kumar, T Senthil; Park, J I; Nou, I S
Applied biochemistry and biotechnology
2014Aug ; 173 ( 8 ) :2254-66.
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Srigopalram, S -
Jayraaj, I A -
Kaleeswaran, B -
Balamurugan, K -
Ranjithkumar, M -
Kumar, T Senthil -
Park, J I -
Nou, I S -
ABSTRACT
Despite great advances in our understanding of the molecular causes of liver cancer, significant gaps still remain in our knowledge of the disease pathogenesis and development of effective strategies for early diagnosis and treatment. The present study was conducted to evaluate the chemopreventive activity of ellagic acid (EA) against experimental liver cancer in rats. This is the first report that implies a possible role of EA in controlling liver cancer through activation of mitochondrial outer membrane permeability via activating proteins such as Bax, bcl-2, cyt-C, and caspase-9, which play important roles in apoptosis. Downregulation of NF-κB, cyclin D1, cyclin E1, matrix metalloproteinases (MMP)-2, MMP-9, and proliferating cell nuclear antigen (PCNA) were noted in EA-treated experimental rats and controlled inflammation mediated liver cancer when compared to the diethylnitrosamine (DEN)-induced group. Transmission electron microscopy (TEM) analysis of the livers of experimental rats demonstrated that EA treatment renovated its internal architecture. Overall, these results demonstrate the value of molecular approaches in identifying the potential role of EA as an effective chemopreventive agent.
Ellagic acid, Diethylnitrosamine, Cell proliferation, Mast cell, PCNA, Caspase, Apoptosis, Mitochondria, Membrane permeability
MESH
Animals, Caspase 3/genetics/immunology, Cell Membrane Permeability/drug effects, Cell Proliferation/*drug effects, Cyclin D1/genetics/immunology, Ellagic Acid/*administration & dosage, Humans, Liver Neoplasms/*drug therapy/genetics/immunology, Male, Mitochondria/*drug effects/immunology, NF-kappa B/genetics/immunology, Rats, Rats, Wistar, bcl-2-Associated X Protein/genetics/immunology
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EA treatment renovated its internal architecture. Overall, these results demonstrate the value of molecular approaches in identifying the potential role of EA as an effective chemopreventive agent.
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DOI
10.1007/s12010-014-1031-y.
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ICD 03
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