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Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells.

Winitthana T, Lawanprasert S, Chanvorachote P - PLoS ONE (2014)

Bottom Line: Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells.Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells.Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

ABSTRACT
Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating system. The present study reveals that treatment of the cancer cells with triclosan at the physiologically related concentrations significantly increased the colony number of the cancer cells assessed by tumor formation assay. Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells. Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated. Furthermore, EMT induced by triclosan treatment was accompanied by the activation of focal adhesion kinase/ATP dependent tyrosine kinase (FAK/Akt) and Ras-related C3 botulinum toxin substrate 1 (Rac1), which enhanced the ability of the cells to migrate and invade. In conclusion, we demonstrated for the first time that triclosan may potentiate cancer cells survival in detached condition and motility via the process of EMT. As mentioned capabilities are required for success in metastasis, the present study provides the novel toxicological information and encourages the awareness of triclosan use in cancer patients.

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Related in: MedlinePlus

Effects of TCS on E-cadherin and EMT markers.(A) Anoikis resistant H460 cells were treated with TCS (0–7.5 µM) for 24 h in detached condition. The level of N-cadherin, E-cadherin, vimentin, slug and snail were determined by western blotting. Blots were reprobed with β-actin to confirm equal loading. (B) The immunoblot signals were quantified by densitometry and mean data from independent experiments were normalized to the results. The data present means of the three independent triplicate samples ± SE. *P<0.05 versus non-treated control.
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pone-0110851-g004: Effects of TCS on E-cadherin and EMT markers.(A) Anoikis resistant H460 cells were treated with TCS (0–7.5 µM) for 24 h in detached condition. The level of N-cadherin, E-cadherin, vimentin, slug and snail were determined by western blotting. Blots were reprobed with β-actin to confirm equal loading. (B) The immunoblot signals were quantified by densitometry and mean data from independent experiments were normalized to the results. The data present means of the three independent triplicate samples ± SE. *P<0.05 versus non-treated control.

Mentions: We next investigated the effect of TCS treatment on EMT markers including N-cadherin, vimentin, snail, and slug. Anoikis resistant H460 cells were treated with non-toxic concentrations of TCS for 24 h and EMT markers were evaluated by western blotting. Figures 4A and B show that the expression level of E-cadherin was significantly decreased in response to TCS treatment in a concentration-dependent manner. In addition, TCS significantly enhanced the increase of N-cadherin, vimentin, slug, and snail. The expression of snail was significantly enhanced by TCS treatment at 5 and 7.5 µM in a dose-dependent manner, while the expression of slug was only significantly induced by the treatment with TCS at 7.5 µM. These results suggested that TCS increased EMT phenotypes in these cells.


Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells.

Winitthana T, Lawanprasert S, Chanvorachote P - PLoS ONE (2014)

Effects of TCS on E-cadherin and EMT markers.(A) Anoikis resistant H460 cells were treated with TCS (0–7.5 µM) for 24 h in detached condition. The level of N-cadherin, E-cadherin, vimentin, slug and snail were determined by western blotting. Blots were reprobed with β-actin to confirm equal loading. (B) The immunoblot signals were quantified by densitometry and mean data from independent experiments were normalized to the results. The data present means of the three independent triplicate samples ± SE. *P<0.05 versus non-treated control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199721&req=5

pone-0110851-g004: Effects of TCS on E-cadherin and EMT markers.(A) Anoikis resistant H460 cells were treated with TCS (0–7.5 µM) for 24 h in detached condition. The level of N-cadherin, E-cadherin, vimentin, slug and snail were determined by western blotting. Blots were reprobed with β-actin to confirm equal loading. (B) The immunoblot signals were quantified by densitometry and mean data from independent experiments were normalized to the results. The data present means of the three independent triplicate samples ± SE. *P<0.05 versus non-treated control.
Mentions: We next investigated the effect of TCS treatment on EMT markers including N-cadherin, vimentin, snail, and slug. Anoikis resistant H460 cells were treated with non-toxic concentrations of TCS for 24 h and EMT markers were evaluated by western blotting. Figures 4A and B show that the expression level of E-cadherin was significantly decreased in response to TCS treatment in a concentration-dependent manner. In addition, TCS significantly enhanced the increase of N-cadherin, vimentin, slug, and snail. The expression of snail was significantly enhanced by TCS treatment at 5 and 7.5 µM in a dose-dependent manner, while the expression of slug was only significantly induced by the treatment with TCS at 7.5 µM. These results suggested that TCS increased EMT phenotypes in these cells.

Bottom Line: Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells.Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells.Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

ABSTRACT
Alteration of cancer cell toward mesenchymal phenotype has been shown to potentiate tumor aggressiveness by increasing cancer cell metastasis. Herein, we report the effect of triclosan, a widely used antibacterial agent found in many daily products, in enhancing the epithelial-to-mesenchymal transition (EMT) in aggressive anoikis resistant human H460 lung cancer cells. EMT has been long known to increase abilities of the cells to increase migration, invasion, and survival in circulating system. The present study reveals that treatment of the cancer cells with triclosan at the physiologically related concentrations significantly increased the colony number of the cancer cells assessed by tumor formation assay. Also, the mesenchymal-like morphology and decrease in cell-to-cell adhesion were observed in triclosan-treated cells. Importantly, western blot analysis revealed that triclosan-treated cells exhibited decreased E-cadherin, while the levels of EMT markers, namely N-cadherin, vimentin, snail and slug were found to be significantly up-regulated. Furthermore, EMT induced by triclosan treatment was accompanied by the activation of focal adhesion kinase/ATP dependent tyrosine kinase (FAK/Akt) and Ras-related C3 botulinum toxin substrate 1 (Rac1), which enhanced the ability of the cells to migrate and invade. In conclusion, we demonstrated for the first time that triclosan may potentiate cancer cells survival in detached condition and motility via the process of EMT. As mentioned capabilities are required for success in metastasis, the present study provides the novel toxicological information and encourages the awareness of triclosan use in cancer patients.

Show MeSH
Related in: MedlinePlus