A novel celecoxib analog UTX-121 inhibits HT1080 cell invasion by modulating membrane-type 1 matrix metalloproteinase

Hirari Yamahana; Takahisa Takino; Yoshio Endo; Hisatsugu Yamada; Takeshi Suzuki; Yoshihiro Uto

doi:10.1016/j.bbrc.2019.10.092

A novel celecoxib analog UTX-121 inhibits HT1080 cell invasion by modulating membrane-type 1 matrix metalloproteinase

Biochem Biophys Res Commun. 2020 Jan 1;521(1):137-144. doi: 10.1016/j.bbrc.2019.10.092. Epub 2019 Oct 16.

Authors

Hirari Yamahana¹, Takahisa Takino², Yoshio Endo³, Hisatsugu Yamada¹, Takeshi Suzuki⁴, Yoshihiro Uto⁵

Affiliations

¹ Graduate School of Technology, Industrial and Social Science, Tokushima University, Tokushima, 770-8506, Japan.
² Division of Education for Global Standard, Institute of Liberal Arts and Science, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. Electronic address: ttakino@staff.kanazawa-u.ac.jp.
³ Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
⁴ Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
⁵ Graduate School of Technology, Industrial and Social Science, Tokushima University, Tokushima, 770-8506, Japan. Electronic address: uto.yoshihiro@tokushima-u.ac.jp.

PMID: 31629465
DOI: 10.1016/j.bbrc.2019.10.092

Abstract

We designed and synthesized a celecoxib derivative UTX-121 to enhance its anti-tumor activity. Similar to celecoxib, this compound could also inhibit matrix metalloproteinase (MMP)-9 activity. In addition, UTX-121 suppressed membrane-type 1 MMP (MT1-MMP)-mediated pro-MMP-2 activation by disturbing the cell surface expression of MT1-MMP. UTX-121 also impeded the glycosylation of cell surface proteins, resulting in the suppression of cell attachment to fibronectin. This inhibition by UTX-121 caused the reduction of fibronectin-stimulated focal adhesion kinase activation, Akt activation, and cell migration. Consequently, UTX-121 treatment significantly inhibited fibronectin-induced HT1080 cell invasion into the Matrigel. UTX-121 may be a potent lead compound that can be used to develop a novel anti-tumor drug.

Keywords: COX; Cell adhesion; Invasion; MMP; MT1-MMP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Celecoxib / analogs & derivatives
Celecoxib / chemistry
Celecoxib / pharmacology*
Cell Adhesion / drug effects
Cell Survival / drug effects
Humans
Matrix Metalloproteinase 14 / metabolism*
Molecular Structure
Tumor Cells, Cultured

Substances

Anti-Inflammatory Agents, Non-Steroidal
MMP14 protein, human
Matrix Metalloproteinase 14
Celecoxib