The Cockayne syndrome group B DNA repair protein as an anti-cancer target

  • Authors:
    • Y. Lu
    • Sridhar Mani
    • Ekambar R. Kandimalla
    • Dong Yu
    • Sudhir Agrawal
    • J. Christopher States
    • David B. Bregman
  • View Affiliations

  • Published online on: December 1, 2001     https://doi.org/10.3892/ijo.19.6.1089
  • Pages: 1089-1097
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Abstract

Cells from individuals with Cockayne syndrome (CS) have a defect in transcription-coupled DNA repair (TCR), which rapidly corrects certain DNA lesions located on the transcribed strand of active genes. Despite this DNA repair defect, individuals with CS (of which there are two complementation groups, CSA and CSB) do not demonstrate an elevated incidence of cancer. Recently, we demonstrated that disruption of the CSB gene reduces the spontaneous tumor rate in cancer predisposed Ink4a/ARF-/- mice as well as causing their embryo fibroblasts to proliferate more slowly and be more sensitive to UV-induced apoptosis. In the present study we characterized phosphorothioate backbone antisense oligodeoxynucleotides (AOs) that reduced the levels of CSB mRNA in A2780/CP70 ovarian carcinoma cells. The AOs caused the cells to proliferate more slowly and made them more sensitive to either cisplatin or oxaliplatin. The AOs also enhanced the cytotoxicity of hydrogen peroxide and γ-radiation, both of which can induce oxidative DNA lesions, which are subject to TCR. The AOs did not potentiate the cytotoxicity of topotecan, which induces DNA strand breaks. Chemically modified () AOs (MBOs) targeting CSB were able to potentiate the anti-tumor effect of cisplatin against A2780/CP70 tumor xenografts formed in nude mice. The MBOs enabled a non-toxic (3 mg/kg) dose of cisplatin to have the same degree of anti-tumor efficacy as a more toxic (5 mg/kg) cisplatin dose. Collectively, these results suggest that the CSB gene product may be viewed as an anti-cancer target.

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December 2001
Volume 19 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lu Y, Mani S, Kandimalla ER, Yu D, Agrawal S, States JC and Bregman DB: The Cockayne syndrome group B DNA repair protein as an anti-cancer target. Int J Oncol 19: 1089-1097, 2001.
APA
Lu, Y., Mani, S., Kandimalla, E.R., Yu, D., Agrawal, S., States, J.C., & Bregman, D.B. (2001). The Cockayne syndrome group B DNA repair protein as an anti-cancer target. International Journal of Oncology, 19, 1089-1097. https://doi.org/10.3892/ijo.19.6.1089
MLA
Lu, Y., Mani, S., Kandimalla, E. R., Yu, D., Agrawal, S., States, J. C., Bregman, D. B."The Cockayne syndrome group B DNA repair protein as an anti-cancer target". International Journal of Oncology 19.6 (2001): 1089-1097.
Chicago
Lu, Y., Mani, S., Kandimalla, E. R., Yu, D., Agrawal, S., States, J. C., Bregman, D. B."The Cockayne syndrome group B DNA repair protein as an anti-cancer target". International Journal of Oncology 19, no. 6 (2001): 1089-1097. https://doi.org/10.3892/ijo.19.6.1089