title: Carboxamide analog ITR-284 evokes apoptosis and inhibits migration ability in human lung adenocarcinoma A549 cells.
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.
authors.affiliation: Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40447, Taiwan, R.O.C.
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Chia-An
authors.initials: CA
authors.lastname: Lin
authors.affiliation: School of Nutrition and Health Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Medicinal Chemistry Laboratory, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan, R.O.C.
authors.forename: Yen-Fang
authors.initials: YF
authors.lastname: Wen
authors.affiliation: Human Genetic Center, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Tsai
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C545715:N-(2-dimethylaminoethyl)-4,8-dihydrobenzo(1,2-b,4,5-b')dithiophene-2-carboxamide; D017382:Reactive Oxygen Species; D013876:Thiophenes