Biomol Ther.  2014 Nov;22(6):540-546. 10.4062/biomolther.2014.081.

Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

• Kim HJ
• Park MK
• Kim SY
• Lee CH

• KMID: 2170596
• DOI: http://doi.org/10.4062/biomolther.2014.081

Abstract

The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

Keyword

Ketotifen; Migration; Invasion; MDA-MB-231; HT-1080

MeSH Terms

Blotting, Western
Breast Neoplasms
Cell Movement
Extracellular Matrix
Fibrosarcoma
Ketotifen*
Matrix Metalloproteinase 9
Mortality
Neoplasm Metastasis
Ketotifen
Matrix Metalloproteinase 9