Effects of chemotherapeutics on expression of cellular pH regulators in small cell lung cancer (SCLC) cell lines

Event Abstract Back to Event Effects of chemotherapeutics on expression of cellular pH regulators in small cell lung cancer (SCLC) cell lines Lukas Klameth1*, Martin Svoboda2, Theresia Thalhammer2, Ulrike Olszewski1 and Gerhard Hamilton1 1 Ludwig Boltzmann Cluster for Translational Oncology, Austria 2 Medical University of Vienna, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Austria Background and aims. Small Cell Lung cancer (SCLC) is characterized by a poor prognosis, because of late diagnosis and early resistance to standard chemotherapy. Since under hypoxic conditions, tumor cells irreversibly shift their energy metabolism from oxidative phosphorylation towards an increased anaerobic glycolysis, the pH regulatory proteins carbonic anhydrases IX (CA IX) and XII (CA XII), sodium proton exchanger 1 (NHE1) and monocarboxylate transporters 1 (MCT1) and 4 (MCT4) may provide new chemotherapeutic targets. However, targeting these proteins may also be influenced by previously applied chemotherapeutic drugs. Methods. The influence of cisplatin, etoposide and topotecan on the expression of these pH regulating proteins in two chemoresistant SCLC cell lines, namely DMS-153 and NCI-H417, and one chemonaïve SCLC cell line, NCI-H526, was assessed by qPCR. Protein levels of CA IX were analyzed by Western Blot and cytotoxicity was measured using MTT assays. Results. Regulation of gene expression depended on the degree of chemoresistance of the respective cell line. CAIX mRNA downregulation in response to cisplatin treatment was seen in the higher resistant cell lines DMS-153 and NCI-H417 (0.4-fold each), while CA XII mRNA expression is upregulated 2.5-fold in sensitive NCI-H526 cells. NHE1 gene expression decreases in DMS-153 cells (0.5-fold), while sensitive NCI-H526 and more chemoresistant NCI-H417 cells have an upregulated NHE1 gene expression to 2.5 and 1.5-fold, respectively, in response to cisplatin treatment. No change in MCT1 gene expression was seen in chemoresistant cell lines in response to cisplatin, while a 0.5-fold reduction was observed in the chemonaïve cell line. Etoposide is able to increase MCT 1 expression by 2-fold in NCI-H526 cells, but has no effects in DMS-153 and NCI-H417 cells. MCT4 gene expression decreases in NCI-H526 cells (0.2-fold) but increases in DMS-153 and NCI-H417 cells by 2.2 and 1.8-fold, respectively. Conclusions / Discussion. Standard chemotherapy in SCLC modulates the expression of pH-regulating proteins and this has to be considered for a possible second-line therapy involving inhibitors directed to CA IX, CA XII, MCT1, MCT4 and/or NHE1. Acknowledgements This work was funded in part by the “Medical Scientific Fund of the Mayor of the City of Vienna“, project number 11016. Keywords: Carbonic Anhydrases, pH control, Small Cell Lung Cancer, monocarboxylate transporters, sodium proton exchanger, Chemotherapy, Adjuvant Conference: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer, Garching, Germany, 10 Oct - 12 Oct, 2013. Presentation Type: Abstract Topic: 9. Acidity as a target for antitumor therapy Citation: Klameth L, Svoboda M, Thalhammer T, Olszewski U and Hamilton G (2014). Effects of chemotherapeutics on expression of cellular pH regulators in small cell lung cancer (SCLC) cell lines. Front. Pharmacol. Conference Abstract: 4th Annual Meeting of the International Society of Proton Dynamics in Cancer. doi: 10.3389/conf.fphar.2014.61.00025 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Jan 2014; Published Online: 07 Feb 2014. * Correspondence: Mr. Lukas Klameth, Ludwig Boltzmann Cluster for Translational Oncology, Vienna, 1090, Austria, lukas.klameth@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lukas Klameth Martin Svoboda Theresia Thalhammer Ulrike Olszewski Gerhard Hamilton Google Lukas Klameth Martin Svoboda Theresia Thalhammer Ulrike Olszewski Gerhard Hamilton Google Scholar Lukas Klameth Martin Svoboda Theresia Thalhammer Ulrike Olszewski Gerhard Hamilton PubMed Lukas Klameth Martin Svoboda Theresia Thalhammer Ulrike Olszewski Gerhard Hamilton Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.