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Article

N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells

  • Authors:
    • Gabriella Brum
    • Thomas Carbone
    • Eric Still
    • Vendita Correia
    • Kevin Szulak
    • David Calianese
    • Charles Best
    • Garret Cammarata
    • Katelyn Higgins
    • Fang Ji
    • Wen Di
    • Yinsheng Wan
  • View Affiliations / Copyright

    Affiliations: Department of Biology, Providence College, Providence, RI 02918, USA, Department of Obstetrics and Gynecology, Renji Hospital of Shanghai Jiaotong University Medical School, Shanghai 200001, P.R. China
  • Pages: 211-218
    |
    Published online on: October 26, 2012
       https://doi.org/10.3892/ijo.2012.1680
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Abstract

Doxorubicin has been used clinically to treat various types of cancer, and yet the molecular mode of actions of doxorubicin remains to be fully unraveled. In this study, we investigated the effect of doxorubicin on cultured ovarian cancer cells (CaOV3). MTT assay data showed that doxorubicin inhibits cell proliferation in a time- and dose-dependent manner. Phagokinetic cell motility assay data indicated that doxorubicin inhibits both basal level and EGF-induced cell migration in CaOV3 cells. Confocal microscopic data revealed that doxorubicin induces reorganization of cytoskeletal proteins including actin, tubulin and vimentin. Doxorubicin induces phosphorylation of p53 at Ser15 and 20, acetylation of p53 and ATM activation. Doxorubicin also induces phosphorylation of histone H2AX at Ser139. Interestingly, doxorubicin also inhibits mTOR activity, measured by phosphorylation of S6 ribosomal protein. Pretreatment of CaOV3 cells with antioxidant N-acetylcysteine (NAC), but not pyrrolidine dithiocarbamate (PDTC) potentiates doxorubicin-induced phosphorylation of p53 and ATM. Collectively, we conclude that doxorubicin induces ATM/p53 activation leading to reorganization of cytoskeletal networks, inhibition of mTOR activity, and inhibition of cell proliferation and migration. Our data also suggest that removal of oxidants by antioxidants such as NAC may enhance the efficacy of doxorubicin in vivo.
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Copy and paste a formatted citation
Spandidos Publications style
Brum G, Carbone T, Still E, Correia V, Szulak K, Calianese D, Best C, Cammarata G, Higgins K, Ji F, Ji F, et al: N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. Int J Oncol 42: 211-218, 2013.
APA
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D. ... Wan, Y. (2013). N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. International Journal of Oncology, 42, 211-218. https://doi.org/10.3892/ijo.2012.1680
MLA
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D., Best, C., Cammarata, G., Higgins, K., Ji, F., Di, W., Wan, Y."N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells". International Journal of Oncology 42.1 (2013): 211-218.
Chicago
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D., Best, C., Cammarata, G., Higgins, K., Ji, F., Di, W., Wan, Y."N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells". International Journal of Oncology 42, no. 1 (2013): 211-218. https://doi.org/10.3892/ijo.2012.1680
Copy and paste a formatted citation
x
Spandidos Publications style
Brum G, Carbone T, Still E, Correia V, Szulak K, Calianese D, Best C, Cammarata G, Higgins K, Ji F, Ji F, et al: N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. Int J Oncol 42: 211-218, 2013.
APA
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D. ... Wan, Y. (2013). N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells. International Journal of Oncology, 42, 211-218. https://doi.org/10.3892/ijo.2012.1680
MLA
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D., Best, C., Cammarata, G., Higgins, K., Ji, F., Di, W., Wan, Y."N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells". International Journal of Oncology 42.1 (2013): 211-218.
Chicago
Brum, G., Carbone, T., Still, E., Correia, V., Szulak, K., Calianese, D., Best, C., Cammarata, G., Higgins, K., Ji, F., Di, W., Wan, Y."N-acetylcysteine potentiates doxorubicin-induced ATM and p53 activation in ovarian cancer cells". International Journal of Oncology 42, no. 1 (2013): 211-218. https://doi.org/10.3892/ijo.2012.1680
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