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Geraniin suppresses tumor cell growth and triggers apoptosis in human glioma via inhibition of STAT3 signaling

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Abstract

Natural phytochemicals are attracting increasing interest as anticancer agents. The aim of this study is to evaluate the therapeutic potential of geraniin, a major ellagitannin extracted from Geranium sibiricum L., in human glioma. Human U87 and LN229 glioma cells were treated with different concentrations of geraniin, and cell viability, apoptosis, and gene expression were assessed. The involvement of STAT3 signaling in the action of geraniin was examined. We found that geraniin treatment for 48 h significantly (P < 0.05) impaired the phosphorylation of STAT3 and reduced the expression of downstream target genes Bcl-xL, Mcl-1, Bcl-2, and cyclin D1. Exposure to geraniin led to a concentration-dependent decline in cell viability and increase in apoptosis in glioma cells, but had no significant impact on the viability of normal human astrocytes. Measurement of caspase-3 activity showed that geraniin-treated U87 and LN229 cells showed a 1.8–2.5-fold higher caspase-3 activity than control cells. Overexpression of constitutively active STAT3 significantly (P < 0.05) reversed geraniin-mediated growth suppression and apoptosis, which was accompanied by restoration of Bcl-xL, Mcl-1, Bcl-2, and cyclin D1 expression. In an xenograft tumor mouse model, geraniin treatment significantly retarded tumor growth and induced apoptosis. Western blot analysis confirmed the suppression of STAT3 phosphorylation in glioma xenograft tumors by geraniin. Taken together, these data suggest that geraniin exerts growth-suppressive and pro-apoptotic effects on glioma cells via inhibition of STAT3 signaling and may have therapeutic benefits in malignant gliomas.

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Authors and Affiliations

  1. Encephalopathy Division, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China

    Zhong Ren

  2. Liver Disease Division, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China

    Wenshuang Zou

  3. Clinical Training Center, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China

    Junfeng Cui

  4. Department of Orthopaedic Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Luping Liu

  5. Department of Nuclear Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Yang Qing

  6. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China

    Yongmei Li

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  1. Zhong Ren
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  2. Wenshuang Zou
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  3. Junfeng Cui
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  4. Luping Liu
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  5. Yang Qing
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Correspondence to Yongmei Li.

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Ren, Z., Zou, W., Cui, J. et al. Geraniin suppresses tumor cell growth and triggers apoptosis in human glioma via inhibition of STAT3 signaling. Cytotechnology 69, 765–773 (2017). https://doi.org/10.1007/s10616-017-0085-4

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  • DOI: https://doi.org/10.1007/s10616-017-0085-4

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