Antitumor potential of novel betulin derivative on human A375 melanoma cell line

Abstract

Event Abstract Back to Event Antitumor potential of novel betulin derivative on human A375 melanoma cell line Mirna Bulatovic1*, Marija Mojic1, Goran Kaludjerovic2, Djordje Miljkovic1, Stanislava Stosic-Grujicic1, Reinhard Paschke2, Sanja Mijatovic1 and Danijela Maksimovic-Ivanic1 1 Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Serbia 2 Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, Germany There is increasing evidence that chronic inflammation causes most of chronic diseases, including cancer and that one out of seven malignant tumors today is a result of chronic inflammation. Betulinic acid is a betulin derivative, pentacyclic triterpene with lupane skeleton, which is one of the first natural product isolated from birch bark. It has a number of pharmacological effects including anti-inflamatory, antitumor and anti-HIV. Betulinic acid induces mitochondrial pathway of apoptosis by directly interacting with permeability transition pore complex and through production of ROS which facilitates opening of the pore. It downregulates NF-κB controlled proinflammatory genes such as COX-2, MMP9 and iNOS. In this study we evaluated antimelanoma effect of novel betulin derivative, 3-O-ethylcarbamate-28-O-acetyl-betulin. We found that novel compound significantly reduced viability of iNOS+ A375 human melanoma cells, with IC50 value four times lower than betulinic acid. Cell cycle analysis demonstrated considerable accumulation of cells in subG phase after two days of treatment with IC50 dose, while Ann/PI staining demonstrated that cells undergo apoptosis much faster under treatment with novel compound compared to betulinic acid. Real-time PCR analysis revealed enhanced caspase 9 and pro-apoptotic Bax gene expression accompanied with general caspase activation confirmed by apostat staining. DHR and DAF-FM staining demonstrated massive production of reactive oxygen and nitrogen species indicating that mechanism of cell death induction is not related with inhibition of iNOS. In conclusion, novel betulin compound has a much stronger antimelanoma effect realized through mitochondrial dependent apoptosis synchronized with production of reactive oxygen and nitrogen species. Keywords: A375 melanoma cells, Apoptosis, Betulinic acid, Nitric Oxide, Reactive Oxygen Species Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Bulatovic M, Mojic M, Kaludjerovic G, Miljkovic D, Stosic-Grujicic S, Paschke R, Mijatovic S and Maksimovic-Ivanic D (2013). Antitumor potential of novel betulin derivative on human A375 melanoma cell line. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00715 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: 17 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Mirna Bulatovic, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia, mirnabulatovic@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 Mirna Bulatovic Marija Mojic Goran Kaludjerovic Djordje Miljkovic Stanislava Stosic-Grujicic Reinhard Paschke Sanja Mijatovic Danijela Maksimovic-Ivanic Google Mirna Bulatovic Marija Mojic Goran Kaludjerovic Djordje Miljkovic Stanislava Stosic-Grujicic Reinhard Paschke Sanja Mijatovic Danijela Maksimovic-Ivanic Google Scholar Mirna Bulatovic Marija Mojic Goran Kaludjerovic Djordje Miljkovic Stanislava Stosic-Grujicic Reinhard Paschke Sanja Mijatovic Danijela Maksimovic-Ivanic PubMed Mirna Bulatovic Marija Mojic Goran Kaludjerovic Djordje Miljkovic Stanislava Stosic-Grujicic Reinhard Paschke Sanja Mijatovic Danijela Maksimovic-Ivanic 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.