Chia-Jen Lee1, Chia-Herng Yue2, Yu-Jie Lin3, Yu-Yu Lin3, Shao-Hsuan Kao4, Jer-Yuh Liu5, Yieng-How Chen6. 1. Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C. 2. Department of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C. 3. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, R.O.C. 4. 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. 5. 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. 6. 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.
Abstract
UNLABELLED: 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. CONCLUSION: 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. Copyright
UNLABELLED: 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 humanlung 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. CONCLUSION: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. Copyright
Authors: Valeria Napolitano; Agnieszka Dabrowska; Kenji Schorpp; André Mourão; Emilia Barreto-Duran; Malgorzata Benedyk; Pawel Botwina; Stefanie Brandner; Mark Bostock; Yuliya Chykunova; Anna Czarna; Grzegorz Dubin; Tony Fröhlich; Michael Hölscher; Malwina Jedrysik; Alex Matsuda; Katarzyna Owczarek; Magdalena Pachota; Oliver Plettenburg; Jan Potempa; Ina Rothenaigner; Florian Schlauderer; Klaudia Slysz; Artur Szczepanski; Kristin Greve-Isdahl Mohn; Bjorn Blomberg; Michael Sattler; Kamyar Hadian; Grzegorz Maria Popowicz; Krzysztof Pyrc Journal: Cell Chem Biol Date: 2022-01-11 Impact factor: 9.039