br Acknowledgments br Introduction Cancer is a deadly diseas
Introduction Cancer is a deadly disease of uncontrolled cell division and has the potential to invade or spread to other parts of the body and affects normal functioning of the vital organs. Nowadays cancer is considered as leading cause of human death in all over the world and its burden will continue to increase due to continuous growth and ageing of world's population . Leukemia is one of the major types of cancer, affecting significant segments of the human population, especially children and adolescents. Based on diagnosis the most common forms of leukemia are acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia and chronic lymphocytic leukemia . Previously, it has been well documented that amino acids serve as regulatory molecules that modulate numerous cellular functions and provide substrates for protein synthesis in both cancer as well as normal cells . Several auxotrophic cancers including leukemia nutritionally depend on host to fulfil their amino acids requirements. Therapeutics selectively targeting deprivation of these amino acids are currently used in effective treatment strategy for some cancers and numerous are still under intensive clinical investigations . Arginase (l-Arginine amidinohydrolase, E.C. 126.96.36.199) is a metallo-enzyme hydrolyses l-arginine into non-proteinogenic amino SB 366791 receptor l-ornithine and urea. Since last few years, this enzyme is widely investigated for starvation therapy of hepatocellular carcinoma and melanoma. In the recent past, researchers have paid much attention and also explored arginase against other arginine-auxotrophic cancers such as pancreatic cancer , prostate cancer , leukemia , glioblastoma , breast cancer  and non-Hodgkin's lymphoma . Many arginine auxotrophic cancers have shown lack expression of argininosuccinate synthetase-1 (ASS1) due to which they are unable to synthesize their own arginine. Indeed, they required massive amount of arginine for malignant proliferation and metastasis . Therapeutic application of arginase hydrolyses l-arginine of circulating system into l-ornithine and urea . l-Arginine depletion leads nutritional starvation, resulting in inhibition of biosynthesis of DNA, RNA, and proteins which causes apoptosis of cancer cells. In the contrary, normal cells remain unaffected due to endogenous biosynthesis of arginine . Beside in cancer chemotherapy, arginase is also involved in the treatment of hyper-argininemia; a genetic metabolic disorder occurs due to the deficiency of liver arginase , . In recent years, many scientists have reported purification and characterization of arginase from bacteria , fungi , plants  and animal tissues . But relative higher antigenicity, short serum half-life, rapid proteolysis and lower thermal stability of currently available arginases are restricted its clinical applications. Previously, several efforts have been made to mitigate these therapeutic limitations but results are still unsatisfactory. Therefore, a new arginase which possesses potent and selective anticancer activity with prolonged serum half-life and strong proteolytic tolerance is essentially required for successful therapeutical applications. Endophytes are the microorganisms that live inside the plants and exert many advantageous effects in host plants. Now a day's, endophytes are explored to discover new compounds having extensive biotechnological and pharmaceutical applications , . Although, several researchers have evaluated terrestrial microbes for therapeutically active arginase but in existing literature, no such reports are available which have explored endophytes for arginase enzyme with potential chemotherapeutic application. Therefore, in the present communication, we report purification and characterization of an extracellular arginase from endophytic P. aeruginosa IH2. Further, purified arginase has been evaluated for anticancer activity against panel of human cancer cell lines. Purified enzyme showed the highest anticancer activity against human leukemic cell line HL-60 and no substantial cytotoxicity was observed with human noncancer cells (HEK-293 and FR-2). Therefore, further antileukemic potential of purified arginase was investigated against human promyelocytic leukemia HL-60 cells, using various cellular and sub-cellular assays.