TY - JOUR
T1 - Novel suppressive effects of ketotifen on migration and invasion of MDA-MB-231 and HT-1080 cancer cells
AU - Kim, Hyun Ji
AU - Park, Mi Kyung
AU - Kim, Soo Youl
AU - Lee, Chang Hoon
N1 - Publisher Copyright:
© 2014 The Korean Society of Applied Pharmacology.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - HT-1080
KW - Invasion
KW - Ketotifen
KW - MDA-MB-231
KW - Migration
UR - http://www.scopus.com/inward/record.url?scp=84912565419&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2014.081
DO - 10.4062/biomolther.2014.081
M3 - Article
AN - SCOPUS:84912565419
SN - 1976-9148
VL - 22
SP - 540
EP - 546
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 6
ER -