www.pelagiaresearchlibrary.com t Available online a Pelagia Research Library European Journal of Experimental Biology, 2013, 3(5):301-306 ISSN: 2248 –9215 CODEN (USA): EJEBAU 301 Pelagia Research Library Cytotoxic and apoptotic activity of leinamycin Produced by Streptomyces atroolivaceous THS-44 isolate from Iraqi soli Hayfa H Hassani, Thura A Kadhim and Ahmed M AL-Shimary ( Department of Biology, College of Science, University of Baghdad, Baghdad, Al-Jadirya, Iraq) Iraqi Center for Cancer and Medical Genetic Researches, University of Al-Mustansirya, Baghdad, Iraq ______________________________________________________________________________ ABSTRACT Leinamycin is a thiol dependent DNA alkylating agent which shows very potent activity against various cancer cell lines. This natural compound forms guanine adducts (N7) in DNA which are converted into a basic sites and simultaneously generates Reactive Oxygen Species (ROS), to produce DNA strand breaks in human cancer cells. In present study, eight different strains isolated from Iraqi soils were taxonomically assigned as Streptomyces.atroolivaceous. Remarkably the strain named as THS-44 was distinguished in productivity in comparison with other strains; the amount of leinamycin was 50.98 mg/l. In this study, we assessed the cytotoxic activity of leinamycin against RD and ANM3 cancer cell line in compare with REF cell line as a normal control. leinamycin revealed a potent activity against growth of both RD , and AMN3 cell lines with inhibition rate (93.56%, and 86.67%) respectively at 100mg/ml as a highest concentration. Moreover, leinamycin from THS-44 strain was mediate apoptotic effects on cancer cells without affecting on the normal cell line REF; a clear cut difference in the % of fragmented DNA was found between both RD, and AMN3 malignant cells, and REF normal cell line (89.16, and 83.1466, and 13.75; p< 0.001, and p< 0.001) respectively after exposure to 4.5μg/ml, leinamycin for 24hrs of incubation period. Key words: Leinamycin, S.atroolivaceous, Antiproliferation, Natural product, Apoptosis. _____________________________________________________________________________________________ INTRODUCTION For thousands of years, natural products have played an important role throughout the world in treating and preventing human diseases [1]. Among 43,000 bioactive natural products, approximately 10,000 are bioactive metabolites produced by produced by Actinomycetes. it was reported that 6,550 are produced by Streptomyces species [2; 3] Leinamycin (LNM) is natural product produced by several Streptomyces atroolivaceus species which is characterized by an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a 18-member macrolactam ring, a molecular architecture that has not been found to date in any other natural product [4]. Early studies by the discoverers of leinamycin showed that attack of the thiol on the 1,2-dithiolan-3-one 1-oxide in leinamycin initiates conversion of heterocycle to a 1,2-oxathiolan-5-one , which undergoes further rearrangement to an episulfonium ion [5]. This episulfonium ion associates noncovalently with duplex DNA. And alkylates the N7-position of guanine residues in double-stranded DNA in highly efficiency [6].