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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 inhibited the migration of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on MDA-MB-231 cell migration. MDAMB-231 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation. (B) Photographs of migrated MDA-MB-231 cells. (C) Effect of ketotifen on HT-1080 cell migration. HT-1080 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (D) Photographs of migrated HT-1080 cells. (E) Effect of ketotifen on migration of TPA-treated HT-1080 cells. HT-1080 cells were treated with vehicle or increasing concentrations (1, 5, 10, 25 μM) of ketotifen and with TPA (20 nM) for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (F) Photographs of migrated HT-1080 cells. For the migration assay, the lower-chamber transwells were coated with fibronectin (10 μg/ml). After incubation, the cells on the bottom side of the filter were fixed, stained by Diff-quick, and subsequently counted in four randomly chosen high-power (200×) fields. The lower chambers contained 3% FBS except NT (not treated with 3% FBS). *p<0.05, **p<0.01.
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f2-bt-22-540: Ketotifen inhibited the migration of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on MDA-MB-231 cell migration. MDAMB-231 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation. (B) Photographs of migrated MDA-MB-231 cells. (C) Effect of ketotifen on HT-1080 cell migration. HT-1080 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (D) Photographs of migrated HT-1080 cells. (E) Effect of ketotifen on migration of TPA-treated HT-1080 cells. HT-1080 cells were treated with vehicle or increasing concentrations (1, 5, 10, 25 μM) of ketotifen and with TPA (20 nM) for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (F) Photographs of migrated HT-1080 cells. For the migration assay, the lower-chamber transwells were coated with fibronectin (10 μg/ml). After incubation, the cells on the bottom side of the filter were fixed, stained by Diff-quick, and subsequently counted in four randomly chosen high-power (200×) fields. The lower chambers contained 3% FBS except NT (not treated with 3% FBS). *p<0.05, **p<0.01.

Mentions: We examined the effects of ketotifen on the migration of MDA-MB-231 and HT-1080 cancer cells known to be highly metastatic. The migration of MDA-MB-231 cells was dose-dependently suppressed by ketotifen (Fig. 2A, 2B); that of HT-1080 cells was suppressed only at 25 μM (Fig. 2C, 2D). The inhibitory effects of ketotifen on MDA-MB-231 cells were stronger than on HT-1080 cells. TPA-induced migration of HT-1080 was much more efficiently suppressed by ketotifen than was FBS-induced migration of the same cells (Fig. 2E, 2F).


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 inhibited the migration of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on MDA-MB-231 cell migration. MDAMB-231 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation. (B) Photographs of migrated MDA-MB-231 cells. (C) Effect of ketotifen on HT-1080 cell migration. HT-1080 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (D) Photographs of migrated HT-1080 cells. (E) Effect of ketotifen on migration of TPA-treated HT-1080 cells. HT-1080 cells were treated with vehicle or increasing concentrations (1, 5, 10, 25 μM) of ketotifen and with TPA (20 nM) for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (F) Photographs of migrated HT-1080 cells. For the migration assay, the lower-chamber transwells were coated with fibronectin (10 μg/ml). After incubation, the cells on the bottom side of the filter were fixed, stained by Diff-quick, and subsequently counted in four randomly chosen high-power (200×) fields. The lower chambers contained 3% FBS except NT (not treated with 3% FBS). *p<0.05, **p<0.01.
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Related In: Results  -  Collection

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f2-bt-22-540: Ketotifen inhibited the migration of MDA-MB-231 and HT-1080 cells. (A) Effect of ketotifen on MDA-MB-231 cell migration. MDAMB-231 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation. (B) Photographs of migrated MDA-MB-231 cells. (C) Effect of ketotifen on HT-1080 cell migration. HT-1080 cells (5×104/well) were treated with vehicle or increasing concentrations (1, 5, 25 μM) of ketotifen for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (D) Photographs of migrated HT-1080 cells. (E) Effect of ketotifen on migration of TPA-treated HT-1080 cells. HT-1080 cells were treated with vehicle or increasing concentrations (1, 5, 10, 25 μM) of ketotifen and with TPA (20 nM) for 24 h. Cells migrated through the membrane after 6 h of incubation were stained and photographed. (F) Photographs of migrated HT-1080 cells. For the migration assay, the lower-chamber transwells were coated with fibronectin (10 μg/ml). After incubation, the cells on the bottom side of the filter were fixed, stained by Diff-quick, and subsequently counted in four randomly chosen high-power (200×) fields. The lower chambers contained 3% FBS except NT (not treated with 3% FBS). *p<0.05, **p<0.01.
Mentions: We examined the effects of ketotifen on the migration of MDA-MB-231 and HT-1080 cancer cells known to be highly metastatic. The migration of MDA-MB-231 cells was dose-dependently suppressed by ketotifen (Fig. 2A, 2B); that of HT-1080 cells was suppressed only at 25 μM (Fig. 2C, 2D). The inhibitory effects of ketotifen on MDA-MB-231 cells were stronger than on HT-1080 cells. TPA-induced migration of HT-1080 was much more efficiently suppressed by ketotifen than was FBS-induced migration of the same cells (Fig. 2E, 2F).

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