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Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity.

Niu PG, Zhang YX, Shi DH, Liu Y, Chen YY, Deng J - PLoS ONE (2015)

Bottom Line: The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition.The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased.The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Fujian Provincial Maternal and Child Health Hospital, Fuzhou, Fujian, China.

ABSTRACT
The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.

No MeSH data available.


Related in: MedlinePlus

Effects of cardamonin on the phosphorylation of mTOR, S6K1 and the expression of E-cadherin, Snail.LLC cells were treated with different drugs for 24 h, and then the total protein was extracted. Analysis of protein expression of mTOR, S6K1, p-mTOR p-S6K1, E-cadherin and Snail was performed by Western Blot method. Expressions of mTOR, p-mTOR, S6K1, p-S6K1, E-cadherin, Snail and actin were showed as the immunoblot band (n = 3).
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pone.0127778.g005: Effects of cardamonin on the phosphorylation of mTOR, S6K1 and the expression of E-cadherin, Snail.LLC cells were treated with different drugs for 24 h, and then the total protein was extracted. Analysis of protein expression of mTOR, S6K1, p-mTOR p-S6K1, E-cadherin and Snail was performed by Western Blot method. Expressions of mTOR, p-mTOR, S6K1, p-S6K1, E-cadherin, Snail and actin were showed as the immunoblot band (n = 3).

Mentions: Western blotting was used to explore the underlying mechanism by which cardamonin exerted its actions. The mTOR pathway is frequently activated in various cancers, which is account for cell growth, proliferation and metastasis. We found that the phosphorylation of mTOR and S6K1 were significantly decreased by cardamonin, indicating that cardamonin effectively inhibited mTOR signal pathway. The expression of E-cadherin is partially regulated by mTOR pathway. mTOR mediated loss of E-cadherin decreases the cellular adhesion, resulting in an increased invasive and metastatic potential. Our results found that cardamonin and rapamycin induced mTOR inhibition was accompanied by increased E-cadherin expression. Then the protein level of Snail, an immediate upstream inhibitory transcription regulator of E-cadherin, was determined to clarify the effect of cardamonin on E-cadherin expression. As expected, the protein amount of Snail was decreased following cardamonin and rapamycin treatment (Fig 5).


Cardamonin Inhibits Metastasis of Lewis Lung Carcinoma Cells by Decreasing mTOR Activity.

Niu PG, Zhang YX, Shi DH, Liu Y, Chen YY, Deng J - PLoS ONE (2015)

Effects of cardamonin on the phosphorylation of mTOR, S6K1 and the expression of E-cadherin, Snail.LLC cells were treated with different drugs for 24 h, and then the total protein was extracted. Analysis of protein expression of mTOR, S6K1, p-mTOR p-S6K1, E-cadherin and Snail was performed by Western Blot method. Expressions of mTOR, p-mTOR, S6K1, p-S6K1, E-cadherin, Snail and actin were showed as the immunoblot band (n = 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440626&req=5

pone.0127778.g005: Effects of cardamonin on the phosphorylation of mTOR, S6K1 and the expression of E-cadherin, Snail.LLC cells were treated with different drugs for 24 h, and then the total protein was extracted. Analysis of protein expression of mTOR, S6K1, p-mTOR p-S6K1, E-cadherin and Snail was performed by Western Blot method. Expressions of mTOR, p-mTOR, S6K1, p-S6K1, E-cadherin, Snail and actin were showed as the immunoblot band (n = 3).
Mentions: Western blotting was used to explore the underlying mechanism by which cardamonin exerted its actions. The mTOR pathway is frequently activated in various cancers, which is account for cell growth, proliferation and metastasis. We found that the phosphorylation of mTOR and S6K1 were significantly decreased by cardamonin, indicating that cardamonin effectively inhibited mTOR signal pathway. The expression of E-cadherin is partially regulated by mTOR pathway. mTOR mediated loss of E-cadherin decreases the cellular adhesion, resulting in an increased invasive and metastatic potential. Our results found that cardamonin and rapamycin induced mTOR inhibition was accompanied by increased E-cadherin expression. Then the protein level of Snail, an immediate upstream inhibitory transcription regulator of E-cadherin, was determined to clarify the effect of cardamonin on E-cadherin expression. As expected, the protein amount of Snail was decreased following cardamonin and rapamycin treatment (Fig 5).

Bottom Line: The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition.The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased.The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Fujian Provincial Maternal and Child Health Hospital, Fuzhou, Fujian, China.

ABSTRACT
The mammalian target of rapamycin (mTOR) regulates the motility and invasion of cancer cells. Cardamonin is a chalcone that exhibits anti-tumor activity. The previous study had proved that the anti-tumor effect of cardamonin was associated with mTOR inhibition. In the present study, the anti-metastatic effect of cardamonin and its underlying molecule mechanisms were investigated on the highly metastatic Lewis lung carcinoma (LLC) cells. The proliferation, invasion and migration of LLC cells were measured by MTT, transwell and wound healing assays, respectively. The expression and activation of mTOR- and adhesion-related proteins were assessed by Western blotting. The in vivo effect of cardamonin on the metastasis of the LLC cells was investigated by a mouse model. Treated with cardamonin, the proliferation, invasion and migration of LLC cells were significantly inhibited. The expression of Snail was decreased by cardamonin, while that of E-cadherin was increased. In addition, cardamonin inhibited the activation of mTOR and its downstream target ribosomal S6 kinase 1 (S6K1). Furthermore, the tumor growth and its lung metastasis were inhibited by cardamonin in C57BL/6 mice. It indicated that cardamonin inhibited the invasion and metastasis of LLC cells through inhibiting mTOR. The metastasis inhibitory effect of cardamonin was correlated with down-regulation of Snail and up-regulation of E-cadherin.

No MeSH data available.


Related in: MedlinePlus