View : 117 Download: 0

Everolimus exerts anticancer effects through inhibiting the interaction of matrix metalloproteinase-7 with syndecan-2 in colon cancer cells

Title
Everolimus exerts anticancer effects through inhibiting the interaction of matrix metalloproteinase-7 with syndecan-2 in colon cancer cells
Authors
Eok-SooOhLeeSeohyeonJangBoheeHwangJisunYejinChoSubinYangHyeonjuYunJi-HyeShinDong HaeWeontae
Ewha Authors
오억수신동해황지선장보희
SCOPUS Author ID
오억수scopus; 신동해scopus; 황지선scopus; 장보희scopus
Issue Date
2024
Journal Title
American Journal of Physiology - Cell Physiology
ISSN
0363-6143JCR Link
Citation
American Journal of Physiology - Cell Physiology vol. 326, no. 4, pp. C1067 - C1079
Keywords
colon cancereverolimusmatrix metalloproteinase-7syndecan 2protein drug interaction
Publisher
American Physiological Society
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer. © 2024 the American Physiological Society.
DOI
10.1152/ajpcell.00669.2023
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

BROWSE