title: In vitro pro-oxidant action of Methotrexate in presence of white light.
abstract: Methotrexate (MTX) an anti-cancer drug as well as a photosensitizer is able to generate reactive oxygen species (ROS). Cu (II) is present associated with chromatin in cancer cells and has been shown to be capable of mediating the action of several anti-cancer drugs through production of ROS. The objective of the present study is to determine Cu (II) mediated anti-cancer mechanism of MTX under photoilluminated condition as well as alone, using alkaline single cell gel electrophoresis (comet assay). We have shown that cellular DNA breakage was enhanced when Cu (II) is used with MTX as compared to MTX alone. It is also shown that MTX alone as well as in combination with Cu (II) is able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS but the pattern of inhibition was differential as was also demonstrated by plasmid nicking assay. Thus, we can say that MTX exhibit pro-oxidant action in presence of white light which gets elevated in presence of Cu (II). Hence, we propose that the mobilization of endogenous copper is possibly involved in killing of cancer cells by MTX during chemo-radio therapy besides acting as antifolate.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslin University, Aligarh, UP 202 002, India.
authors.forename: Sandesh
authors.initials: S
authors.lastname: Chibber
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Hassan
authors.forename: Mohd
authors.initials: M
authors.lastname: Farhan
authors.forename: Imrana
authors.initials: I
authors.lastname: Naseem
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D020552:Comet Assay; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D053960:DNA Breaks; D006801:Humans; D008027:Light; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008727:Methotrexate / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D016877:Oxidants / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress; D017319:Photosensitizing Agents / Q000737:chemistry / Q000633:toxicity*; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D016877:Oxidants; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D003300:Copper; D008727:Methotrexate