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Molecules 2014, 19(3), 2862-2876; doi:10.3390/molecules19032862
Article

Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

1,†, 2,†, 1,* , 1, 1 and 1
Received: 6 January 2014; in revised form: 25 February 2014 / Accepted: 26 February 2014 / Published: 5 March 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract: Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.
Keywords: telmisartan; A549 cells; lung cancer; peroxisome proliferator-activated receptor-γ (PPARγ); intercellular adhesion molecule-1 (ICAM-1); matrix metalloprotease-9 (MMP-9) telmisartan; A549 cells; lung cancer; peroxisome proliferator-activated receptor-γ (PPARγ); intercellular adhesion molecule-1 (ICAM-1); matrix metalloprotease-9 (MMP-9)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Li, J.; Chen, L.; Yu, P.; Liu, B.; Zhu, J.; Yang, Y. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells. Molecules 2014, 19, 2862-2876.

AMA Style

Li J, Chen L, Yu P, Liu B, Zhu J, Yang Y. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells. Molecules. 2014; 19(3):2862-2876.

Chicago/Turabian Style

Li, Juan; Chen, Lin; Yu, Ping; Liu, Bin; Zhu, Jiang; Yang, Ye. 2014. "Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells." Molecules 19, no. 3: 2862-2876.


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