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Naringenin (Citrus Flavonone) Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinoma Cells

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Pathology & Oncology Research

Abstract

Search for new substances with antiproliferative activity and apoptosis inducing potential towards HepG2 cells is important since HCC is notoriously resistant to conventional chemotherapy. Dietary phytochemicals with significant anti-proliferative and apoptosis inducing potential are considered as agents promising for cancer therapy. Naringenin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong cytotoxic activity in numerous types of cancer cells. However, the detailed molecular mechanisms of its antiproliferative effects and apoptosis induction are still unclear. In this study, we investigated antiproliferative and apoptosis-inducing effect of naringenin in human hepatocellular carcinoma HepG2 cells. Naringenin was shown to inhibit the proliferation of HepG2 cells resulted partly from an accumulation of cells in the G0/G1 and G2/M phase of the cell cycle. Naringenin induced a rapid accumulation of p53, which might account for the naringenin-induced G0/G1 and G2/M phase arrests in Hep G2 cells. In addition, naringenin have been shown to induce apoptosis as evidenced by nuclei damage and increased proportion of apoptotic cells detected by flow cytometry analysis. Naringenin triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, subsequent release of cytochrome C, and sequential activation of caspase-3. Our results showed that naringenin had inhibitory effect on the growth of HepG2 cell line through inhibition of cell proliferation and apoptosis induction. The elucidation of the drug targets of naringenin on inhibition of tumor cells growth should enable further development of naringenin for liver cancer therapy.

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Acknowledgements

We wish to thank Prof. C.M. Elinos-Báez, Universidad Nacional Autónoma de México, Mexico for her gift of antibodies against Bcl-2 and Bax; Prof. S. Soddu, Regina Elena Cancer Institute, Italy for her kind gift of anti p53; Prof. Haider Raza, UAE University, UAE for her kind gift of antibodies against caspase-3; Prof. Ronald Jemmerson, Department of Microbiology, Northwestern University for her kind gift of the antibody against cytochrome C.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India

    Duraikannu Arul & Perumal Subramanian

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  1. Duraikannu Arul
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  2. Perumal Subramanian
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Correspondence to Duraikannu Arul.

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Arul, D., Subramanian, P. Naringenin (Citrus Flavonone) Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinoma Cells. Pathol. Oncol. Res. 19, 763–770 (2013). https://doi.org/10.1007/s12253-013-9641-1

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  • DOI: https://doi.org/10.1007/s12253-013-9641-1

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