Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors

  • Authors:
    • Kaijie Wu
    • Jin Zeng
    • Lei Li
    • Jinhai Fan
    • Dong Zhang
    • Yan Xue
    • Guodong Zhu
    • Lin Yang
    • Xinyang Wang
    • Dalin He
  • View Affiliations

  • Published online on: June 1, 2010     https://doi.org/10.3892/or_00000794
  • Pages: 1545-1552
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Abstract

Silibinin, a naturally occurring flavanone isolated from milk thistle extract, has been shown to possess strong anticancer efficacy against both androgen-dependent and androgen-independent prostate cancer, wherein it inhibits not only cell growth, but also cell invasion and metastasis. Inhibitory effects of silibinin on prostate cancer invasion, motility and migration were previously observed in the highly bone metastatic ARCaPM cell line; however, mechanisms of such efficacy are not completely elucidated. The epithelial-to-mesenchymal transition (EMT) is a crucial step in the progression of prostate cancer, reversal or inhibition of EMT by drugs thus provides a new approach to prostate cancer therapy. In the present study, we found that silibinin treatment resulted in the up-regulation of cytokeratin-18 and down-regulation of vimentin and MMP2, which was consistent with morphologic reversal of EMT phenotype leading to be epithelial. Moreover, we found that silibinin could inhibit the nuclear factor κB (NF-κB) p50 translocation via the up-regulation of IκBα protein, and possibly subsequently down-regulated the expression of two major EMT regulators, ZEB1 and SLUG transcription factors. Overall these findings demonstrate silibinin was able to reverse EMT to suppress the invasive property of metastatic prostate cancer cells at the transcriptional level.

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June 2010
Volume 23 Issue 6

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

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APA
Wu, K., Zeng, J., Li, L., Fan, J., Zhang, D., Xue, Y. ... He, D. (2010). Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors . Oncology Reports, 23, 1545-1552. https://doi.org/10.3892/or_00000794
MLA
Wu, K., Zeng, J., Li, L., Fan, J., Zhang, D., Xue, Y., Zhu, G., Yang, L., Wang, X., He, D."Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors ". Oncology Reports 23.6 (2010): 1545-1552.
Chicago
Wu, K., Zeng, J., Li, L., Fan, J., Zhang, D., Xue, Y., Zhu, G., Yang, L., Wang, X., He, D."Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors ". Oncology Reports 23, no. 6 (2010): 1545-1552. https://doi.org/10.3892/or_00000794