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 output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalArchives of Pharmacal Research
DOIs
Publication statusAccepted/In press - 2017 Dec 1

Fingerprint

Triple Negative Breast Neoplasms
Cells
Neoplasm Metastasis
Phosphorylation
Chemotherapy
Breast Neoplasms
Tumors
CDC2 Protein Kinase
M Phase Cell Cycle Checkpoints
Drug Therapy
Neoplasms
Serine Proteinase Inhibitors
Oncology
G2 Phase
Cell growth
Metalloproteases
Progesterone Receptors
Growth
nafamostat
Epidermal Growth Factor Receptor

Keywords

  • Cell cycle
  • Metastasis
  • Nafamostat mesilate
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

Cite this

Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells. / Mander, Sunam; You, Dong Joo; Park, Sumi; Kim, Dong Hwi; Yong, Hyo Jeong; Kim, Dong-Sik; Ahn, Curie; Kim, Yun Hee; Seong, Jae Young; Hwang, Jong-Ik.

In: Archives of Pharmacal Research, 01.12.2017, p. 1-14.

Research output: Contribution to journalArticle

Mander, Sunam ; You, Dong Joo ; Park, Sumi ; Kim, Dong Hwi ; Yong, Hyo Jeong ; Kim, Dong-Sik ; Ahn, Curie ; Kim, Yun Hee ; Seong, Jae Young ; Hwang, Jong-Ik. / Nafamostat mesilate negatively regulates the metastasis of triple-negative breast cancer cells. In: Archives of Pharmacal Research. 2017 ; pp. 1-14.
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