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Icaritin Sensitizes Human Glioblastoma Cells to TRAIL-Induced Apoptosis

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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered to be one of the most promising candidates in research on treatments for cancer, because it induces apoptosis in a wide variety of cancer cells but not in most normal human cell types. However, many cells including glioblastoma (GBM) cells are resistant to TRAIL-induced apoptosis, which limits the potential application of TRAIL in cancer therapy. Icaritin, a hydrolytic product of icariin from Epimedium Genus, has been identified as a potential therapeutic and preventive agent in renal cell carcinoma and breast cancer. In this study, we investigated whether Icaritin treatment could modulate TRAIL-induced apoptosis in GBM. The effect of icaritin on TRAIL sensitivity was assessed in human GBM U87 and U373 cells. The underlying regulatory cascades were approached by biochemical and pharmacological strategies. We found that nontoxic concentration of icaritin alone had no significant effect on the level of apoptosis, but a combination treatment of TRAIL and icaritin caused a significantly more profound apoptosis. The sensitization was accompanied by c-FLIP down-regulation and inhibition of NF-κB activity. Studies have further demonstrated that silencing NF-κB alone was sufficient to down-regulate c-FLIP expression and sensitized both tested cells to TRAIL-induced apoptosis. These data suggest that icaritin sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent c-FLIP expression, providing in vitro evidence supporting the notion that icaritin is a potential sensitizer of TRAIL in anticancer therapy against human GBM.

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Authors and Affiliations

  1. Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Hongxing Han

  2. Department of Neurology, Linyi People’s Hospital, Linyi, Shandong, China

    Hongxing Han

  3. Department of Neurology, Provincial Hospital of Shandong University, Jinan, Shandong, China

    Bo Xu

  4. Department of Neurology, The Second Affiliated Hospital, Medical College of Qingdao University, Qingdao, Shandong, China

    Bo Xu

  5. Department of Neurosurgery, Huangdao Traditional Chinese Medicine Hospital, Qingdao, Shandong, China

    Pengzhi Hou

  6. Department of Radiology, Qingdao Hiser Medical Center, Qingdao, Shandong, China

    Chuanwu Jiang

  7. Department of Radiology, Provincial Hospital of Shandong University, Jinan, Shandong, China

    Chuanwu Jiang

  8. Department of Neurosurgery, Qingdao Hiser Medical Center, Qingdao, Shandong, China

    Longxi Liu, Yunxu Zhang & Yongji Liu

  9. Department of Neurology, Qingdao Hiser Medical Center, Qingdao, Shandong, China

    Ming Tang & Xiuli Yang

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  1. Hongxing Han
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Correspondence to Yongji Liu.

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Hongxing Han and Bo Xu have contributed equally to this study.

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Han, H., Xu, B., Hou, P. et al. Icaritin Sensitizes Human Glioblastoma Cells to TRAIL-Induced Apoptosis. Cell Biochem Biophys 72, 533–542 (2015). https://doi.org/10.1007/s12013-014-0499-y

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