title: Redox cycling of Cu(II) by 6-mercaptopurine leads to ROS generation and DNA breakage: possible mechanism of anticancer activity.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A. M. University, Aligarh, U.P., 202002, India.
authors.forename: Sayeed Ur
authors.initials: SU
authors.lastname: Rehman
authors.forename: Haseeb
authors.initials: H
authors.lastname: Zubair
authors.forename: Tarique
authors.initials: T
authors.lastname: Sarwar
authors.forename: Mohammed Amir
authors.initials: MA
authors.lastname: Husain
authors.forename: Hassan Mubarak
authors.initials: HM
authors.lastname: Ishqi
authors.forename: Shamshun
authors.initials: S
authors.lastname: Nehar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tabish
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D003300:Copper / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015122:Mercaptopurine / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D003300:Copper; D015122:Mercaptopurine