title: Antitumor activity of acriflavine in lung adenocarcinoma cell line A549.
abstract: Aim/Materials and Methods: In order to develop better drugs against non-small cell lung cancer (NSCLC), we screened a variety of compounds and treated the human lung adenocarcinoma cell line A549 with different drug concentrations. We then examined the cell viability using the MTT assay.
  
  
  RESULTS
  Data show that a new candidate drug, acriflavine (ACF), suppresses the viability of A549 cells in a concentration- and time-dependent manner. Flow cytometry analysis revealed that ACF significantly caused cell growth arrest in the G2/M phase on A549 cells. Moreover, ACF decreased Bcl-2 expression and increased Bax expression. The content of cleaved poly(ADP-ribose)polymerase-1 (PARP-1) and caspase-3 are significantly increased. These findings suggest that ACF is cytotoxic against A549 cells and suppresses A549 cells growth through the caspase-3 activation pathway. In the in vivo test, nude mice bearing A549 cells xenografts by intravenous injection were randomly assigned into two groups: control and experimental group. Treatment was initiated 10 days after implantation and intraperitoneal injection of 0.9% normal saline or 2 mg/kg of ACF was continued daily for five weeks. ACF treatment significantly decreased tumor size and tumor spots on lung surface of tumor-bearing mice.
  
  
  CONCLUSIONS
  ACF can inhibit cell growth in A549 cells. Our results may assist on the delineation of the mechanism(s) leading to NSCLC cell growth inhibition and provide a new antitumor strategy against NSCLC.
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Herng
authors.initials: CH
authors.lastname: Yue
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. yh7chen@thu.edu.tw jyl@mail.cmu.edu.tw kaosh@csmu.edu.tw.
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Kao
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C. yh7chen@thu.edu.tw jyl@mail.cmu.edu.tw kaosh@csmu.edu.tw.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan, R.O.C. yh7chen@thu.edu.tw jyl@mail.cmu.edu.tw kaosh@csmu.edu.tw.
authors.forename: Yieng-How
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000167:Acriflavine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000891:Anti-Infective Agents, Local; D000970:Antineoplastic Agents; D000167:Acriflavine
keywords: A549; Acriflavine (ACF); lung adenocarcinoma