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White light-mediated Cu (II)–5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study

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Tumor Biology

Abstract

5-Fluorouracil (5-FU) is a potent photosensitizer used in colon and rectal cancers. 5-FU on galvanostatic electrolysis or radiation-induced oxidation of aqueous solution yields N1–C5-linked dimmer hydrate of 5-FU. Copper is presently associated with chromatin; in cancer cells the concentration of copper is very high. It has been shown to be capable of mediating the action of several anticancer drugs through the production of reactive oxygen species (ROS). The objective of the present study is to determine the Cu (II)-mediated anticancer mechanism of 5-FU under photo-illumination as well as 5-FU alone. We have shown that a pro-oxidant action was enhanced when Cu (II) was used with 5-FU as compared to 5-FU alone. This may be due to the inhibition of dimerization of 5-FU when present in combination with Cu (II) under photo-illumination. It was also shown that 5-FU alone as well as in combination with Cu (II) was able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS. Moreover, the results of Fourier-transformed infrared spectra lead to the conclusion that the dimerization of 5-FU was inhibited when used in combination with Cu (II). It was due to the interaction of 5-FU with Cu (II). Hence, we propose that during chemoradiotherapy with 5-FU, the endogenous copper is mobilized by 5-FU, leading to the generation of ROS which cause oxidative stress and possibly cancer cell death by apoptosis.

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Acknowledgments

The authors sincerely acknowledge the financial assistance provided by the University Grant Commission, New Delhi, under SAP program, DST-FIST, and the facilities provided by Department of Biochemistry, Aligarh Muslim University. We are also thankful to Professor M. Mushfiq, Department of Chemistry, Aligarh Muslim University, Aligarh, for helping us in working out a reaction mechanism.

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  1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, U.P-202002, India

    Sandesh Chibber, Mohd Farhan, Iftekhar Hassan & Imrana Naseem

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  1. Sandesh Chibber
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  2. Mohd Farhan
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Correspondence to Imrana Naseem.

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Chibber, S., Farhan, M., Hassan, I. et al. White light-mediated Cu (II)–5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study. Tumor Biol. 32, 881–892 (2011). https://doi.org/10.1007/s13277-011-0189-y

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  • DOI: https://doi.org/10.1007/s13277-011-0189-y

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