Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53

  • Authors:
    • See-Hyoung Park
    • Jung Han Lee
    • Jonathan S. Berek
    • Mickey C.-T. Hu
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  • Published online on: August 4, 2014     https://doi.org/10.3892/ijo.2014.2579
  • Pages: 1691-1698
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Abstract

Auranofin is a gold-containing compound classified by the World Health Organization as a clinically established rheumatoid arthritis therapeutic agent. Through drug screening for novel anticancer therapeutics, we unexpectedly identified auranofin as a potent anticancer agent against a p53-null ovarian carcinoma SKOV3 cell line. However, the molecular mechanism underlying auranofin-mediated anticancer activity in ovarian cancer cells is basically unknown. Here, we show that auranofin inhibits proliferation and survival of SKOV3 cells in a dose‑ and time‑dependent manner. Auranofin treatment activates the pro-apoptotic caspase-3, increases protein levels of apoptosis-inducing proteins Bax and Bim and reduces the expression of the anti-apoptotic mediator Bcl-2 in SKOV3 cells. Moreover, auranofin downregulates IκB kinase (IKK)-β and promotes nuclear localization and the activation of FOXO3 tumor suppressor, leading to cellular apoptosis in SKOV3 cells. In contrast, silencing FOXO3 diminishes the pro-apoptotic signaling of auranofin in SKOV3 cells. These results suggest that auranofin may induce caspase-3-mediated apoptosis in a FOXO3-dependent manner. The observed upregulation of pro-apoptotic genes and apoptosis in cancer cells without p53 in response to auranofin suggests a novel p53-independent mechanism underlying auranofin-induced apoptosis in ovarian cancer cells.
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October 2014
Volume 45 Issue 4

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

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APA
Park, S., Lee, J.H., Berek, J.S., & Hu, M.C. (2014). Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. International Journal of Oncology, 45, 1691-1698. https://doi.org/10.3892/ijo.2014.2579
MLA
Park, S., Lee, J. H., Berek, J. S., Hu, M. C."Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53". International Journal of Oncology 45.4 (2014): 1691-1698.
Chicago
Park, S., Lee, J. H., Berek, J. S., Hu, M. C."Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53". International Journal of Oncology 45, no. 4 (2014): 1691-1698. https://doi.org/10.3892/ijo.2014.2579