Dilda Pierre J, Hogg Philip J
UNSW Cancer Research Centre, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney 2052, Australia.
Cancer Treat Rev. 2007 Oct;33(6):542-64. doi: 10.1016/j.ctrv.2007.05.001. Epub 2007 Jul 10.
Arsenic is a semi-metal or metalloid with two biologically important oxidation states, As(III) and As(V). As(III), in particular, reacts with closely spaced protein thiols, forming stable cyclic dithioarsinite complexes in which both sulfur atoms are bound to arsenic. It is this reaction that is mostly responsible for arsenics cytotoxicity. Arsenic compounds have been used as medicinal agents for many centuries for the treatment of diseases such as psoriasis, syphilis, and rheumatosis. From the 1700's until the introduction of and use of modern chemotherapy and radiation therapy in the mid 1900's, arsenic was a mainstay in the treatment of leukemia. Concerns about the toxicity of arsenical compounds led eventually to their abandonment for the treatment of cancer. The discovery in the 1980's that arsenic trioxide induces complete remission in a high percentage of patients with acute promyelocytic leukemia has awakened interest in this metalloid for the treatment of human disease. In particular, a new class or organoarsenicals are being trialed for the treatment of hematological malignancies and solid tumors. In this review, we discuss the arsenical-based compounds used in the past and present for the treatment of various forms of cancer. Mechanisms of action and selectivity and acute and chronic toxicities are discussed along with the prospects of this class of molecule.
砷是一种半金属或类金属，有两种对生物学重要的氧化态，即As(III)和As(V)。特别是As(III)，它能与紧密相邻的蛋白质硫醇反应，形成稳定的环状二硫代亚砷酸盐配合物，其中两个硫原子都与砷结合。正是这个反应主要导致了砷的细胞毒性。几个世纪以来，砷化合物一直被用作药物来治疗诸如牛皮癣、梅毒和风湿病等疾病。从18世纪到20世纪中叶现代化疗和放射治疗被引入和使用之前，砷一直是治疗白血病的主要药物。对砷化合物毒性的担忧最终导致它们被弃用于癌症治疗。20世纪80年代发现三氧化二砷能使高比例的急性早幼粒细胞白血病患者完全缓解，这重新唤起了人们对这种类金属用于治疗人类疾病的兴趣。特别是，一类新型有机砷化合物正在试验用于治疗血液系统恶性肿瘤和实体瘤。在这篇综述中，我们讨论了过去和现在用于治疗各种癌症的含砷化合物。同时还讨论了其作用机制、选择性以及急性和慢性毒性，以及这类分子的前景。
