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Archives of Pharmacal Research

, Volume 41, Issue 2, pp 229–242 | Cite as

Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells

  • Sunam Mander
  • Dong-Joo You
  • Sumi Park
  • Dong Hwi Kim
  • Hyo Jeong Yong
  • Dong-Sik Kim
  • Curie Ahn
  • Yun-Hee Kim
  • Jae Young Seong
  • Jong-Ik Hwang
Research Article
  • 183 Downloads

Abstract

Triple-negative breast cancer (TNBC) lacking of oestrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2 is a highly malignant disease which results in a poor prognosis and rare treatment options. Despite the use of conventional chemotherapy for TNBC tumours, resistance and short duration responses limit the treatment efficacy. Therefore, a need exists to develop a new chemotherapy for TNBC. The aim of this study was to examine the anti-cancer effects of nafamostat mesilate (NM), a previously known serine protease inhibitor and highly safe drug on breast cancer cells. Here, we showed that NM significantly inhibits proliferation, migration, and invasion in MDA-MB231 cells, induces G2/M phase cell-cycle arrest, and inhibits the expression of cyclin-dependent kinase 1 (CDK1). Exposure of MDA-MB231 cells to NM also resulted in decreased transcription factor activities accompanied by the regulated phosphorylation of signalling molecules and a decrease in metalloproteinases, the principal modulators of the extracellular environment during cancer progression. Especially, inhibition of TGFβ-stimulated Smad2 phosphorylation and subsequent metastasis-related gene expression, and downregulation of ERK activity may be pivotal mechanisms underlying inhibitory effects of NM on NM inhibits lung metastasis of breast cancer cells and growth of colonized tumours in mice. Taken together, our data revealed that NM inhibits cell growth and metastasis of TNBC cells and indicated that NM is a multi-targeted drug that could be an adjunct therapy for TNBC treatment.

Keywords

Nafamostat mesilate Triple negative breast cancer Cell cycle Metastasis 

Notes

Acknowledgements

This work was supported by a Korea Research Foundation Grant funded by the Ministry of Science, ICT, and Future Planning (MSIP; No. NRF-2016R1A2B1010036).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose.

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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  • Sunam Mander
    • 1
  • Dong-Joo You
    • 1
  • Sumi Park
    • 1
  • Dong Hwi Kim
    • 1
  • Hyo Jeong Yong
    • 1
  • Dong-Sik Kim
    • 2
  • Curie Ahn
    • 3
  • Yun-Hee Kim
    • 4
  • Jae Young Seong
    • 1
  • Jong-Ik Hwang
    • 1
  1. 1.Department of Biomedical Sciences, College of MedicineKorea UniversitySeoulRepublic of Korea
  2. 2.Department of HBP Surgery and Liver Transplantation, College of MedicineKorea UniversitySeoulRepublic of Korea
  3. 3.Transplantation Research Institute, Seoul National UniversitySeoulRepublic of Korea
  4. 4.Molecular Imaging & Therapy BranchResearch Institute of National Cancer CenterGoyangRepublic of Korea

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