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Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

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Abstract

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Ellagic acid (EA) has been known for its chemopreventive activity against various cancers and numerous investigations have shown its apoptotic activity both in vivo and in vitro. The present study was focused to elucidate the anticancerous effect and the mode of action of EA against HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. EA also promoted cell cycle arrest substantially at G2/M phase in HCT-15 cells. The activities of alkaline phosphatase and lactate dehydrogenase were decreased upon EA treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA. In further studies, EA inhibited proliferation-associated markers proliferating cell nuclear antigen and cyclin D1. The induction of apoptosis was accompanied by a strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA. The expression of PI3K and pAkt was down-regulated in EA-treated cells, compared to normal cells. Further, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells that was determined by western blot analysis. Increased annexin V apoptotic cells and DNA fragmentation also accompanied EA-induced apoptosis. In conclusion, EA increased the production of ROS, decreased cell proliferation, and induced apoptosis in HCT-15 cells, and thus can be used as an agent against colon cancer.

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Acknowledgments

The authors S. Umesalma and P. Nagendraprabhu gratefully acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, India for the financial assistance in the form of Senior Research Fellowship.

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The authors declare no conflict of interest.

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  1. Department of Biochemistry, Cell Biology Unit, University of Madras, Maraimalai Campus (Guindy), Chennai, 600 025, Tamil Nadu, India

    Syed Umesalma, Ponnuraj Nagendraprabhu & Ganapasam Sudhandiran

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  1. Syed Umesalma
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Correspondence to Ganapasam Sudhandiran.

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Umesalma, S., Nagendraprabhu, P. & Sudhandiran, G. Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells. Mol Cell Biochem 399, 303–313 (2015). https://doi.org/10.1007/s11010-014-2257-2

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