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Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway

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Abstract

Protein Kinase C (PKC) isozymes are key components involved in cell proliferation and their over activation leads to abnormal tumor growth. PKC follows signalling pathway by activation of downstream gene NF-kB and early transcription factor c-Myc. Over activation of NF-kB and c-Myc gene are also linked with unregulated proliferation of cancer cells. Therefore any agent which can inhibit the activation of Protein kinase C, NF-kB and c-Myc may be useful in reducing cancer progression. To investigate this hypothesis we have tested the effect of ellagic acid on these genes in Dalton’s lymphoma bearing (DL). The role of ellagic acid was also tested in regulation of tumor suppressor gene Transforming growth factor-β1 (TGF-β1). DL mice were treated with three different doses (40, 60 and 80 mg/kg body weight) of ellagic acid. Ascites cells of mice were used for the experiments. Ellagic acid administration to DL mice decreased oxidative stress by reducing lipid peroxidation. Ellagic acid also down regulates the expression of classical isozymes of PKC i.e. PKCα, PKCβ, and PKCγ as well as activity of total PKC and NF-kB, indicating its antitumor action. The anticarcinogenic action of ellagic acid was also confirmed by up regulation of TGF-β1 and down regulation of c-Myc. Lymphoma prevention by ellagic acid is further supported by decrease in cell proliferation, cell viability, ascites fluid accumulation and increase in life span of DL mice. All these findings suggest that ellagic acid prevents the cancer progression by down regulation of PKC signaling pathway leading to cell proliferation.

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Acknowledgments

Research was supported by University Grants Commission, India. Sudha Mishra thanks the University Grant Commission, India, for providing a “Research Fellowship in Science for Meritorious Students”.

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  1. Biochemistry & Molecular Biology Laboratory, Center of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India

    Sudha Mishra & Manjula Vinayak

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  1. Sudha Mishra
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  2. Manjula Vinayak
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Correspondence to Manjula Vinayak.

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Mishra, S., Vinayak, M. Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway. Mol Biol Rep 40, 1417–1428 (2013). https://doi.org/10.1007/s11033-012-2185-8

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