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In vitro pro-oxidant action of Methotrexate in presence of white light

Paper ID Volume ID Publish Year Pages File Format Full-Text
30843 44508 2011 7 PDF Available
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.

► MTX follow a different reaction mechanism when illuminated alone. ► ROS generated by MTX are O2-, H2O2 and OH via different pathway. ► MTX in presence of Cu (II) Fenton like reaction is followed generating hydroxyl radical. ► Mobilization of endogenous copper is possibly involved in killing of cancer cells by MTX.

Keywords
Methotrexate; Cu (II); Reactive oxygen species; Oxidative DNA breakage; Comet assay
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In vitro pro-oxidant action of Methotrexate in presence of white light
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 104, Issue 3, 2 September 2011, Pages 387–393
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us