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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 - Biomol Ther (Seoul) (2014)

Bottom Line: Therefore, considerable effort is being made to inhibit metastasis.The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells.Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion.

View Article: PubMed Central - PubMed

Affiliation: BK21PLUS R-FIND Team, College of Pharmacy, Dongguk University, Seoul 100-715.

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.

No MeSH data available.


Related in: MedlinePlus

Structure of Ketotifen.
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f1-bt-22-540: Structure of Ketotifen.

Mentions: Ketotifen is a first-generation antihistamine with store-operated Ca2+ channel antagonist properties (Fig. 1) (Franzius et al., 1994; Zhang and Berger, 2003). As a calcium influx blocker, ketotifen can induce cell death in an activation-enhanced manner in leukemia cells, mast cells, and breast cancer cells (Gommerman and Berger, 1998; Soboloff and Berger, 2002; Soboloff et al., 2002; Zhang et al., 2002). Ketotifen also reverses MDR1-mediated multidrug resistance in human breast cancer cells in vitro and alleviates cardiotoxicity induced by doxorubicin in vivo (Zhang and Berger, 2003).


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 - Biomol Ther (Seoul) (2014)

Structure of Ketotifen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256034&req=5

f1-bt-22-540: Structure of Ketotifen.
Mentions: Ketotifen is a first-generation antihistamine with store-operated Ca2+ channel antagonist properties (Fig. 1) (Franzius et al., 1994; Zhang and Berger, 2003). As a calcium influx blocker, ketotifen can induce cell death in an activation-enhanced manner in leukemia cells, mast cells, and breast cancer cells (Gommerman and Berger, 1998; Soboloff and Berger, 2002; Soboloff et al., 2002; Zhang et al., 2002). Ketotifen also reverses MDR1-mediated multidrug resistance in human breast cancer cells in vitro and alleviates cardiotoxicity induced by doxorubicin in vivo (Zhang and Berger, 2003).

Bottom Line: Therefore, considerable effort is being made to inhibit metastasis.The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells.Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion.

View Article: PubMed Central - PubMed

Affiliation: BK21PLUS R-FIND Team, College of Pharmacy, Dongguk University, Seoul 100-715.

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.

No MeSH data available.


Related in: MedlinePlus