Rehman Sayeed Ur, Zubair Haseeb, Sarwar Tarique, Husain Mohammed Amir, Ishqi Hassan Mubarak, Nehar Shamshun, Tabish Mohammad
Department of Biochemistry, Faculty of Life Sciences, A. M. University, Aligarh, U.P., 202002, India.
Tumour Biol. 2015 Feb;36(2):1237-44. doi: 10.1007/s13277-014-2743-x. Epub 2014 Oct 25.
6-Mercaptopurine (6MP) is a well-known purine antimetabolite used to treat childhood acute lymphoblastic leukemia and other diseases. Cancer cells as compared to normal cells are under increased oxidative stress and show high copper level. These differences between cancer cells and normal cells can be targeted to develop effective cancer therapy. Pro-oxidant property of 6MP in the presence of metal ions is not well documented. Redox cycling of Cu(II) to Cu(I) was found to be efficiently mediated by 6MP. We have performed a series of in vitro experiments to demonstrate the pro-oxidant property of 6MP in the presence of Cu(II). Studies on human lymphocytes confirmed the DNA damaging ability of 6MP in the presence of Cu(II). Since 6MP possesses DNA damaging ability by producing reactive oxygen species (ROS) in the presence of Cu(II), it may also possess apoptosis-inducing activity by involving endogenous copper ions. Essentially, this would be an alternative and copper-dependent pathway for anticancer activity of 6MP.
6-巯基嘌呤（6MP）是一种著名的嘌呤抗代谢物，用于治疗儿童急性淋巴细胞白血病和其他疾病。与正常细胞相比，癌细胞处于更高的氧化应激状态，且铜含量较高。癌细胞与正常细胞之间的这些差异可作为靶点来开发有效的癌症治疗方法。6MP在金属离子存在下的促氧化特性尚未得到充分记录。发现6MP能有效介导Cu（II）向Cu（I）的氧化还原循环。我们进行了一系列体外实验，以证明6MP在Cu（II）存在下的促氧化特性。对人类淋巴细胞的研究证实了6MP在Cu（II）存在下的DNA损伤能力。由于6MP在Cu（II）存在下通过产生活性氧（ROS）具有DNA损伤能力，它也可能通过涉及内源性铜离子而具有诱导凋亡的活性。从本质上讲，这将是6MP抗癌活性的一条替代性的、依赖铜的途径。
