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Emerging Implications of Nonmammalian Cytosine Deaminases on Cancer Therapeutics

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Abstract

Nonmammalian cytosine deaminases (CDs) have been investigated for last 30 years in the context of cancer therapy. The therapeutic effect of CD is based on its ability to catalyze the conversion of nontoxic prodrug 5-fluorocytosine (5FC) into the anticancer drug 5-fluorouracil (5FU) by deamination of the number 4 carbon of 5FC. This deamination property of CD has been explored to develop innovative therapeutic approach for treatment of cancer. A general overview is needed for the identification of efficient cytosine deaminases for potential use in cancer therapy. In this review, we have discussed about nonmammalian CDs for a variety of prodrug gene/enzyme therapy applications with several recent examples. Finally, we have provided a prospective on the future aspects of CDs and their applications in cancer therapy.

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Abbreviations

5FC:

5-Fluorocytosine

5FU:

5-Fluorouracil

AO:

Acridine orange

CD:

Cytosine deaminase

EB:

Ethidium bromide

FdUDP:

Fluorodeoxyuridine diphosphate

FdUMP:

Fluorodeoxyuridine monophosphate

FdUTP:

Fluorodeoxyuridine triphosphate

FUDP:

Fluorouridine diphosphate

FUdR:

Fluorourodeoxyuridine

FUMP:

Fluorouridine monophosphate

FUTP:

Fluorouridine triphosphate

GCV:

Ganciclovir

GFP:

Green fluorescent protein

GDEPT:

Gene-directed enzyme prodrug therapy

HSV-TK:

Herpes simplex virus thymidine kinase

mAb:

Monoclonal antibody

OPRT:

Orotate phosphoribosyltransferase

PLL:

Poly-l-lysine

RT-PCR:

Reverse transcription polymerase chain reaction

RR:

Ribonucleotide reductase

TK:

Thymidine kinase

TP:

Thymidine phosphorylase

TS:

Thymidine synthase

UPRT:

Uracil phosphoribosyltransferase

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Acknowledgments

The authors acknowledge the financial support of the Department of Biotechnology (nos. BT/49/NE/TBP/2010 and BT/01/NE/PS/08) for the research on gene therapy.

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Authors and Affiliations

  1. Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-39, Assam, India

    Vinod Kumar Yata & Siddhartha Sankar Ghosh

  2. Centre for Nanotechnology, Indian Institute of Technology Roorkee, Uttarakhand-67, Roorkee, India

    P. Gopinath

  3. Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati-39, Guwahati, India

    Siddhartha Sankar Ghosh

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  1. Vinod Kumar Yata
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Correspondence to Siddhartha Sankar Ghosh.

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Yata, V.K., Gopinath, P. & Ghosh, S.S. Emerging Implications of Nonmammalian Cytosine Deaminases on Cancer Therapeutics. Appl Biochem Biotechnol 167, 2103–2116 (2012). https://doi.org/10.1007/s12010-012-9746-0

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