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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

Ketotifen reduced the expression of CDC42, Rac and Rho of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of CDC42, Rac and Rho in MDA-MB-231 cells. MDA-MB-231 cells were treated with ketotifen (1, 5, 25 μM) for 24 h. (B) Effect of ketotifen on expression of CDC42, Rac and Rho in TPA-treated HT-1080 cells. HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Whole-cell lysates (10 μg) were prepared, the protein level was subjected to 10% SDS-PAGE, and the expressions of several proteins were determined by western blotting.
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f4-bt-22-540: Ketotifen reduced the expression of CDC42, Rac and Rho of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of CDC42, Rac and Rho in MDA-MB-231 cells. MDA-MB-231 cells were treated with ketotifen (1, 5, 25 μM) for 24 h. (B) Effect of ketotifen on expression of CDC42, Rac and Rho in TPA-treated HT-1080 cells. HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Whole-cell lysates (10 μg) were prepared, the protein level was subjected to 10% SDS-PAGE, and the expressions of several proteins were determined by western blotting.

Mentions: In the first step of cancer cell migration, lamelipodium extension is regulated by CDC42 and Rac expression, and cell-body contraction is regulated by Rho protein and Rac. Therefore, we examined the effects of ketotifen on the expression of CDC42, Rac, and Rho in MDA-MB-231 and HT-1080 cells, especially since ketotifen inhibited those cells’ migration. In MDA-MB-231 cells, ketotifen treatment suppressed CDC42, Rac and Rho expression (Fig. 4A). The most significant suppression was shown at 25 μM (Fig. 4A). In HT-1080 cells, ketotifen strongly suppressed the expressions of CDC42, Rac and Rho, even at low concentrations (Fig. 4B).


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)

Ketotifen reduced the expression of CDC42, Rac and Rho of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of CDC42, Rac and Rho in MDA-MB-231 cells. MDA-MB-231 cells were treated with ketotifen (1, 5, 25 μM) for 24 h. (B) Effect of ketotifen on expression of CDC42, Rac and Rho in TPA-treated HT-1080 cells. HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Whole-cell lysates (10 μg) were prepared, the protein level was subjected to 10% SDS-PAGE, and the expressions of several proteins were determined by western blotting.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-bt-22-540: Ketotifen reduced the expression of CDC42, Rac and Rho of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of CDC42, Rac and Rho in MDA-MB-231 cells. MDA-MB-231 cells were treated with ketotifen (1, 5, 25 μM) for 24 h. (B) Effect of ketotifen on expression of CDC42, Rac and Rho in TPA-treated HT-1080 cells. HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Whole-cell lysates (10 μg) were prepared, the protein level was subjected to 10% SDS-PAGE, and the expressions of several proteins were determined by western blotting.
Mentions: In the first step of cancer cell migration, lamelipodium extension is regulated by CDC42 and Rac expression, and cell-body contraction is regulated by Rho protein and Rac. Therefore, we examined the effects of ketotifen on the expression of CDC42, Rac, and Rho in MDA-MB-231 and HT-1080 cells, especially since ketotifen inhibited those cells’ migration. In MDA-MB-231 cells, ketotifen treatment suppressed CDC42, Rac and Rho expression (Fig. 4A). The most significant suppression was shown at 25 μM (Fig. 4A). In HT-1080 cells, ketotifen strongly suppressed the expressions of CDC42, Rac and Rho, even at low concentrations (Fig. 4B).

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