Verapamil potentiates temozolomide anticancer efficacy through the intrinsic apoptotic pathway in brain cancer cells

Abstract

Event Abstract Back to Event Verapamil potentiates temozolomide anticancer efficacy through the intrinsic apoptotic pathway in brain cancer cells Farina Hanif1, 2*, Kahkashan Perveen2 and Shabana U. Simjee2, 3 1 The Aga Khan University, Department of Biological and Biomedical Sciences, Pakistan 2 University of Karachi, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, Pakistan 3 University of Karachi, HEJ Research Institute of Chemistry (Neuro-pharmacology Unit), International Center for Chemical and Biological Sciences, Pakistan Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Median survival rates of GBM patients is ranged from 12–15 months. Alkylating agents used for the treatment of GBM have severe side effects. The development of new therapeutic strategies for the management of gliomas is therefore crucial. The aim of the study was to examine the efficacy and mechanism of action of calcium channel blocker Verapamil (VP) and standard chemotherapeutic drug Temozolomide (TMZ) in the treatment of GBM, when used alone and in combination. Human GBM cell line U87 was used as an experimental model. MTT and TUNEL assays were used to detect the growth inhibitory effect and apoptotic activity. Synergy of drugs was assessed using combination index method. The RT-PCR and immunocytochemistry was used to determine the mRNA and protein expression of apoptotic markers i.e. Bax (proapoptotic) and Bcl-2 (antiapoptotic). Both these markers play an important role in mediating intrinsic apoptotic pathway. Results revealed that the combine administration of VP (0.2 mM) and TMZ (0.1 mM) synergistically induced apoptosis of glioblastoma cells (CDI<1). Furthermore RT-PCR and immunocytochemistry data revealed that cooperative apoptosis induction is associated with increase in Bax/Bcl-2 ratio (P < 0.01). Our findings support that the combine administration of VP and TMZ may be therapeutically exploited for the management of GBM. Keywords: Gene Expression, Glioblastoma, Cancer cells, Anticancer efficacy, apoptotic pathway Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Hanif F, Perveen K and Simjee SU (2016). Verapamil potentiates temozolomide anticancer efficacy through the intrinsic apoptotic pathway in brain cancer cells. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00190 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: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Farina Hanif, The Aga Khan University, Department of Biological and Biomedical Sciences, Karachi, Sindh, Pakistan, farina.hanif@hotmail.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 Farina Hanif Kahkashan Perveen Shabana U Simjee Google Farina Hanif Kahkashan Perveen Shabana U Simjee Google Scholar Farina Hanif Kahkashan Perveen Shabana U Simjee PubMed Farina Hanif Kahkashan Perveen Shabana U Simjee 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.