Silibinin, a novel chemokine receptor type 4 antagonist, inhibits chemokine ligand 12-induced migration in breast cancer cells

Yan Wang, Wei Cheng Liang, Wen Liang Pan, Wai Kit Law, Jian Shu Hu, Denis Tsz Ming Ip, Mary Miu Yee Waye, Tzi Bun Ng, David Chi Cheong Wan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Purpose C-X-C chemokine receptor type 4 (CXCR4) signaling has been demonstrated to be involved in cancer invasion and migration; therefore, CXCR4 antagonist can serve as an anti-cancer drug by preventing tumor metastasis. This study aimed to identify the CXCR4 antagonists that could reduce and/or inhibit tumor metastasis from natural products. Methods and results According to the molecular docking screening, we reported here silibinin as a novel CXCR4 antagonist. Biochemical characterization showed that silibinin blocked chemokine ligand 12 (CXCL12)-induced CXCR4 internalization by competitive binding to CXCR4, therefore inhibiting downstream intracellular signaling. In human breast cancer cells MDA-MB-231, which expresses high levels of CXCR4, inhibition of CXCL12-induced chemomigration can be found under silibinin treatment. Overexpression of CXCL12 sensitized MDA-MB-231 cells to the inhibition of silibinin, which was abolished by CXCR4 knockdown. The inhibition of silibinin was also observed in MCF-7/CXCR4 cells rather than MCF-7 cells that express low level of CXCR4. Conclusions Our work demonstrated that silibinin is a novel CXCR4 antagonist that may have potential therapeutic use for prevention of tumor metastasis.

Original languageEnglish (US)
Pages (from-to)1310-1317
Number of pages8
JournalPhytomedicine
Volume21
Issue number11
DOIs
StatePublished - Sep 25 2014

Bibliographical note

Funding Information:
This work was partially supported by GRF (ref no: 474808 ) and RFCID grants (ref no: 08070152 ) to DCW.

Keywords

  • Breast cancer
  • CXCR4 antagonist
  • Chemomigration
  • Molecular docking
  • Silibinin

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