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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 MMP-9 expression of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of MMP-9 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 MMP-9 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. (C) Effect of ketotifen on MMP-9 activity in HT-1080 cells. To test the activity of MMP-9, HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Conditioned media were collected, and gelatin zymography was performed as described in Materials and Methods.
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f5-bt-22-540: Ketotifen reduced MMP-9 expression of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of MMP-9 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 MMP-9 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. (C) Effect of ketotifen on MMP-9 activity in HT-1080 cells. To test the activity of MMP-9, HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Conditioned media were collected, and gelatin zymography was performed as described in Materials and Methods.

Mentions: Next, since ketotifen suppressed the invasion of metastatic MDA-MB-231 and HT-1080 cells, we determined whether it also suppresses MMP-9 expression in those cells (Fig. 3). In the results, ketotifen dose-dependently suppressed the expression of MMP-9 in the MDA-MB-231 and HT-1080 cells (Fig. 5). Ketotifen’s suppressive effects were markedly stronger on the HT-1080 cells than on the MDA-MB-231 cells (Fig. 5A, 5B). And, because MMP-9 is secreted to media, we confirmed the effects of ketotifen on HT-1080 cells’ MMP-9 activities by zymography. The data showed that ketotifen suppressed those activities (Fig. 5C).


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 MMP-9 expression of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of MMP-9 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 MMP-9 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. (C) Effect of ketotifen on MMP-9 activity in HT-1080 cells. To test the activity of MMP-9, HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Conditioned media were collected, and gelatin zymography was performed as described in Materials and Methods.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-bt-22-540: Ketotifen reduced MMP-9 expression of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on expression of MMP-9 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 MMP-9 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. (C) Effect of ketotifen on MMP-9 activity in HT-1080 cells. To test the activity of MMP-9, HT-1080 cells were treated with ketotifen (1, 5, 10, 25 μM) and with TPA (20 nM) for 24 h. Conditioned media were collected, and gelatin zymography was performed as described in Materials and Methods.
Mentions: Next, since ketotifen suppressed the invasion of metastatic MDA-MB-231 and HT-1080 cells, we determined whether it also suppresses MMP-9 expression in those cells (Fig. 3). In the results, ketotifen dose-dependently suppressed the expression of MMP-9 in the MDA-MB-231 and HT-1080 cells (Fig. 5). Ketotifen’s suppressive effects were markedly stronger on the HT-1080 cells than on the MDA-MB-231 cells (Fig. 5A, 5B). And, because MMP-9 is secreted to media, we confirmed the effects of ketotifen on HT-1080 cells’ MMP-9 activities by zymography. The data showed that ketotifen suppressed those activities (Fig. 5C).

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