*Corresponding Author Address: Dr. Nada Z. Mahdi, Department of Biology, College of Science, Al-Mustansiriya University, Baghdad, Iraq; E-mail: nada.zeki @ yahoo.co.uk World Journal of Pharmaceutical Sciences ISSN (Print): 2321-3310; ISSN (Online): 2321-3086 Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.wjpsonline.org/ Original Article Cytotoxicity and apoptosis of glioblastoma multiforme cell line by arginine deiminase purified from a higher productive isolation Enterococcus faecium M1 Nada Z. Mahdi* 1 , Shatha S. Al-Tahan 2 and Nahi Y. Yaseen 3 1 Department of Biology, College of Science, Al-Mustansiriya University, Baghdad, Iraq 2 Department of Biology, College of Science, Baghdad University, Baghdad, Iraq 3 Director General of Iraqi Cancer and Medical Genetic Researches, Al-Mustansiriya University, Baghdad, Iraq Received: 17-06-2016 / Revised: 19-07-2016 / Accepted: 22-07-2016 / Published: 31-07-2016 ABSTRACT Purified arginine deiminase from Enterococcus faecium M1 isolate is the strongest cancer treatment enzyme due to its activity and stability in different environmental conditions. The cytotoxicity of ADI to glioblastoma multiforme (ANG) cancer cell line and rat embryo fibroblast(REF) normal cell line for (24, 48 and 72h) were estimated, the inhibition rate(IR) increased with raising of ADI concentration and incubation period for ANG cell line but these results were opposite for REF cell line that IR decreased with increment of incubation period. Different concentrations (2-1000ng) of enzyme were used, the significant once were between (30-100ng) that they were safe for most cells of REF normal cell line but they inhibited the large numbers of glioblastoma cells, that the IC50 of ADI was 37ng/ml for this cancer cell line during 72h of incubation time and the IR reached to 75.4% after 48h incubation with 100ng/ml of enzyme. The ability of ADI to produce intrinsic mitochondrial apoptosis effect on ANG and REF cell lines was investigated, the results showed that the main reason of cell cytotoxicity was the induction of apoptosis process by ADI enzyme and they were compatible to the results of cytotoxicity test. We concluded that ANG cancer cell line could not produce arginine amino acid thus it was highly sensitive to arginine deprivation by the robust activity of arginine deiminase enzyme, but it was safe for REF normal cell line could produce arginine during the incubation time with enzyme. Keywords: Cytotoxicity, Glioblastoma multiforme, Arginine deiminase, E. faecium INTRODUCTION Glyoblastoma multiforme (GBM) is the most common primary human malignant brain tumor and among the most lethal of all cancers [1]. Despite advances in surgical management, radiotherapy, and development of temozolomide, the median survival for patients is 12–16 months [2,3]. The discovery of anticancer drugs remains a highly challenging endeavor and cancer a hard-to- cure disease [4]. Arginine is required by all tissues in the human body for protein synthesis, and by some tissues for specialized needs. Tumour cells have a high requirement for arginine by enhances tumour growth [5]. Recently in Iraq there is a terrible number of unpublished cancer cases. The idea of overloading cancer cells with amino acids they don't want, and starving them of ones they do, has since proven to be a viable approach to cancer treatment [6]. This treatment attempts to inhibit the growth of, or necrotize the cancer cells by decomposing the nourishment required by the cancer cells and thus by shutting out the source of nourishment from the reach of the cancer cells. Arginine deprivation affects glyoblastoma cell adhesion and could inhibit the invasion process of highly malignant brain tumors [7]. Arginine deiminase regarded as arginine-depleting enzyme and being a potential anticancer agent [8]. Arginine deiminase isolated from a higher productive locally isolated strain Enterococcus faecium M1 is a very potent, stable and effective enzyme when used as a cancer theraputic agent [9]. The aim of this study was designed to investigate the cytotoxicity and apoptosis effect of arginine deiminase enzyme purified from the higher productive Enterococcus faecium M1 isolation on most lethal Glioblastoma multiforme cancer cell line and compare it with the effect of enzyme on Rat embrio fibroblast normal cell line in order to use this robust enzyme as a treatment for the highly malignant brain tumors in the future.