Carboxamide analog ITR-284 evokes apoptosis and inhibits migration ability in human lung adenocarcinoma A549 cells

Yang,Jai-Sing; Lin,Chia-An; Lu,Chi-Cheng; Wen,Yen-Fang; Tsai,Fuu-Jen; Tsai,Shih-Chang

doi:10.3892/or.2017.5374

Carboxamide analog ITR-284 evokes apoptosis and inhibits migration ability in human lung adenocarcinoma A549 cells

Authors:
- Jai-Sing Yang
- Chia-An Lin
- Chi-Cheng Lu
- Yen-Fang Wen
- Fuu-Jen Tsai
- Shih-Chang Tsai
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Affiliations: Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C., School of Nutrition and Health Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C., Medicinal Chemistry Laboratory, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan, R.O.C., Human Genetic Center, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C.
Published online on: January 16, 2017 https://doi.org/10.3892/or.2017.5374
Pages: 1786-1792

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Abstract

Lung adenocarcinoma is the most common type of lung cancer and found in both smokers and non-smokers, but the treatment of lung cancer is limited. ITR-284 has been shown to be a potent carboxamide-derived anticancer agent and to induce apoptosis in leukemia and colon cancer cells. However, little is known whether ITR-284 has anticancer activity in human lung adenocarcinoma cells through induction of apoptosis and suppression of migration in vitro. We showed that ITR-284 inhibited human lung cancer A549 cells using the thiazolyl blue tetrazolium bromide (MTT) assay and evoked apoptosis via the cell cycle distribution at S phase arrest. After treatment with 20 nM ITR-284 for 24 h, apoptotic cells were induced and detected by Annexin V-FITC/PI staining. The production of reactive oxygen species (ROS) was dose-dependently increased in A549 cells caused by ITR-284. The results from immunoblotting analysis showed an elevation of protein levels of p53 and phosphorylation of p53 in A549 cells prior to ITR-284 exposure. Additionally, apoptosis-associated proteins such as Bax, cleaved caspase-3 and cleaved PARP were upregulated after ITR-284 treatment. By wound healing assay, low concentrations (1-5 nM) of ITR-284 exerted a greater effect on inhibition of A549 cell migration. The protein levels of E-cadherin and vimentin, which are the epithelial-mesenchymal transition (EMT) markers, were modulated in ITR-284-treated cells assessed by western blot analysis. Taken together, our data suggest that ITR-284 may be an effective anticancer agent for treating lung adenocarcinoma.

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