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Overexpression of miR-7-1 Increases Efficacy of Green Tea Polyphenols for Induction of Apoptosis in Human Malignant Neuroblastoma SH-SY5Y and SK-N-DZ Cells

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Abstract

Neuroblastoma is an extracranial solid tumor that usually occurs in infants and children. Malignant neuroblastomas remain mostly refractory to currently available chemotherapeutic agents. So, new therapeutic agents and their molecular mechanisms for induction of cell death must be explored for successful treatment of human malignant neuroblastomas. Two polyphenolic compounds, which are abundant in green tea, are (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG) that possess impressive anti-cancer properties. It is not known yet whether EGC and EGCG can modulate the levels of expression of specific microRNAs (miRs) for induction of apoptosis in human malignant neuroblastomas. In this investigation, we revealed that treatment with EGC or EGCG caused induction of apoptosis with significant changes in expression of specific oncogenic miRs (OGmiRs) and tumor suppressor miRs (TSmiRs) in human malignant neuroblastoma SH-SY5Y and SK-N-DZ cell lines. Treatment of both cell lines with either 50 μM EGC or 50 μM EGCG decreased expression of the OGmiRs (miR-92, miR-93, and miR-106b) and increased expression of the TSmiRs (miR-7-1, miR-34a, and miR-99a) leading to induction of extrinsic and intrinsic pathways of apoptosis. Our data also demonstrated that overexpression of miR-93 decreased efficacy while overexpression of miR-7-1 increased efficacy of the green tea polyphenols for induction of apoptosis in both cell lines. In conclusion, our current investigation clearly indicates that overexpression of miR-7-1 can highly potentiate efficacy of EGCG for induction of apoptosis in human malignant neuroblastoma cells.

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Acknowledgments

This work was supported in part by a grant (R01 NS65456) from the National Institutes of Health (Bethesda, MD, USA) and another grant (SCIRF-11-002) from the South Carolina Spinal Cord Injury Research Foundation (Columbia, SC, USA).

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Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29209, USA

    Mrinmay Chakrabarti, Walden Ai & Swapan K. Ray

  2. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Naren L. Banik

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  1. Mrinmay Chakrabarti
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  2. Walden Ai
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  3. Naren L. Banik
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  4. Swapan K. Ray
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Correspondence to Swapan K. Ray.

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Chakrabarti, M., Ai, W., Banik, N.L. et al. Overexpression of miR-7-1 Increases Efficacy of Green Tea Polyphenols for Induction of Apoptosis in Human Malignant Neuroblastoma SH-SY5Y and SK-N-DZ Cells. Neurochem Res 38, 420–432 (2013). https://doi.org/10.1007/s11064-012-0936-5

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  • DOI: https://doi.org/10.1007/s11064-012-0936-5

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