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PTEN over-expression by resveratrol in acute lymphoblastic leukemia cells along with suppression of AKT/PKB and ERK1/2 in genotoxic stress

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Abstract

The bioactive components of dietary phytochemicals are in the spotlight of research institutes, due to their significant antioxidant activities and health-promoting properties. Resveratrol is a polyphenol which is found abundantly in grapes and berries and has long been known as a chemo-preventive agent. The main purpose of this study was to provide a new mechanistic insight into the growth inhibition of acute lymphoblastic leukemia cells by resveratrol along with a DNA damage agent. It was found that the treatment of pre-B ALL cells by resveratrol in the presence or absence of doxorubicin resulted in decreased cell viability and a synergistic increase in cytotoxicity. Cell death was accompanied by a significant increase in phosphorylated p53 at serine 15 and accumulation of PTEN. In addition, resveratrol inhibited the over-expression of p-AKT and p-ERK1/2. These findings clearly demonstrated that resveratrol and doxorubicin synergistically increase the cytotoxicity of pre-B ALL cells via the hyper-activation of two important tumor suppressor proteins and two major signal transduction pathways.

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Acknowledgments

The present authors would like to express their gratitude to Avicenna Research Institute and Tehran University of Medical Sciences for supporting this study. The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Cellular and Molecular Nutrition Department, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

      Arman Ghorbani & Fariba Koohdani

    2. National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Department of Basic Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

      Hamid Zand

    3. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

      Mahmood Jeddi-Tehrani

    4. Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

      Farzad Shidfar

    5. Clinical Nutrition Department, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

      Seyed Ali Keshavarz

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    1. Arman Ghorbani
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    2. Hamid Zand
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    4. Fariba Koohdani
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    Correspondence to Seyed Ali Keshavarz.

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    A. Ghorbani and H. Zand equally contributed to this work.

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    Ghorbani, A., Zand, H., Jeddi-Tehrani, M. et al. PTEN over-expression by resveratrol in acute lymphoblastic leukemia cells along with suppression of AKT/PKB and ERK1/2 in genotoxic stress. J Nat Med 69, 507–512 (2015). https://doi.org/10.1007/s11418-015-0915-7

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    • DOI: https://doi.org/10.1007/s11418-015-0915-7

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