Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma

  • Authors:
    • Zhenkun Ma
    • Wei Liu
    • Jin Zeng
    • Jiancheng Zhou
    • Peng Guo
    • Hongjun Xie
    • Zhao Yang
    • Long Zheng
    • Shan Xu
    • Xinyang Wang
    • Luke S. Chang
    • Dalin He
    • Lei Li
  • View Affiliations

  • Published online on: August 26, 2015     https://doi.org/10.3892/or.2015.4224
  • Pages: 2461-2468
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Abstract

The downstream transcriptional factor of the hedgehog (Hh) pathway, GLI family zinc finger 1 (GLI1), plays a crucial role in regulating tumor progression. In the present study, we demonstrated that silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, exerts its anticancer capabilities by restraining GLI1 function in renal cell carcinoma (RCC) cells in vitro and in vivo. In the present study, we confirmed that silibinin induced growth inhibition of RCC through caspase-dependent apoptosis and downregulation of GLI1 and BCL2, which could be partially reversed by GLI1 overexpression. Moreover, we determined that the decreased GLI1 expression by silibinin was mediated by the mammalian target of rapamycin (mTOR) pathway. The in vivo mouse xenograft study also showed that silibinin significantly reduced RCC tumor growth and specifically targeted the mTOR-GLI1-BCL2 signaling pathway. In conclusion, our findings demonstrated for the first time that silibinin induces apoptosis of RCC cells through inhibition of the mTOR-GLI1‑BCL2 pathway. These findings also indicate that GLI1 is a novel regulator for the potential therapeutic application of silibinin against RCC.
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November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ma Z, Liu W, Zeng J, Zhou J, Guo P, Xie H, Yang Z, Zheng L, Xu S, Wang X, Wang X, et al: Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma. Oncol Rep 34: 2461-2468, 2015.
APA
Ma, Z., Liu, W., Zeng, J., Zhou, J., Guo, P., Xie, H. ... Li, L. (2015). Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma. Oncology Reports, 34, 2461-2468. https://doi.org/10.3892/or.2015.4224
MLA
Ma, Z., Liu, W., Zeng, J., Zhou, J., Guo, P., Xie, H., Yang, Z., Zheng, L., Xu, S., Wang, X., Chang, L. S., He, D., Li, L."Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma". Oncology Reports 34.5 (2015): 2461-2468.
Chicago
Ma, Z., Liu, W., Zeng, J., Zhou, J., Guo, P., Xie, H., Yang, Z., Zheng, L., Xu, S., Wang, X., Chang, L. S., He, D., Li, L."Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma". Oncology Reports 34, no. 5 (2015): 2461-2468. https://doi.org/10.3892/or.2015.4224