Open Access

The pure anti-androgen bicalutamide inhibits cyclin A expression both in androgen-dependent and -independent cell lines

  • Authors:
    • Hiroshi Katayama
    • Teruko Murashima
    • Yoshiko Saeki
    • Yasuko Nishizawa
  • View Affiliations

  • Published online on: March 1, 2010     https://doi.org/10.3892/ijo_00000529
  • Pages: 553-562
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Abstract

We investigated the effects of testosterone and the pure anti-androgen, bicalutamide, on DNA synthesis and cell cycle in androgen-sensitive or -insensitive human and mouse cell lines by 3H-thymidine incorporation, flow cytometry, RT-PCR and Western blotting. In androgen-dependent mouse SC-3 cells, testosterone induced DNA synthesis, shift of cell cycle distribution from G0/G1 to S/G2/M and expression of cyclin A. The induction was preceded by that of fibroblast growth factor 8 (FGF-8), and completely blocked by monoclonal antibody to FGF-8. Dihydrotestosterone (DHT) induced cyclin A expression in androgen-sensitive human prostate cancer cells, but not in androgen-independent cell lines. Bicalutamide almost completely inhibited these androgen-dependent effects both in LNCaP and SC-3 cells, but had no or limited effect on androgen-independent or FGF-8-induced DNA synthesis, and FGF-8 induced cyclin A expression. Interestingly, bicalutamide inhibited both DNA synthesis and the cyclin A expression in androgen-independent human cell lines in serum-free condition. A MEK1/2 inhibitor U0126 blocked both androgen- and rFGF-8-induced DNA synthesis. Overall, bicalutamide inhibits the cyclin A expression possibly by inhibiting FGF-8 mRNA expression and FGF-8 protein secretion but not by inhibiting FGF receptor (FGFR) signalling in androgen-dependent cell lines, and by other mechanisms in androgen-independent cell lines. The results suggest that combination with compounds such as FGFR signalling inhibitors may provide additional benefits to anti-androgens. It is also suggested that cyclin A could be a sensitive marker for androgen-induced cancer growth and for the growth inhibitory effects of anti-androgen.

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March 2010
Volume 36 Issue 3

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

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Spandidos Publications style
Katayama H, Murashima T, Saeki Y and Nishizawa Y: The pure anti-androgen bicalutamide inhibits cyclin A expression both in androgen-dependent and -independent cell lines. Int J Oncol 36: 553-562, 2010
APA
Katayama, H., Murashima, T., Saeki, Y., & Nishizawa, Y. (2010). The pure anti-androgen bicalutamide inhibits cyclin A expression both in androgen-dependent and -independent cell lines. International Journal of Oncology, 36, 553-562. https://doi.org/10.3892/ijo_00000529
MLA
Katayama, H., Murashima, T., Saeki, Y., Nishizawa, Y."The pure anti-androgen bicalutamide inhibits cyclin A expression both in androgen-dependent and -independent cell lines". International Journal of Oncology 36.3 (2010): 553-562.
Chicago
Katayama, H., Murashima, T., Saeki, Y., Nishizawa, Y."The pure anti-androgen bicalutamide inhibits cyclin A expression both in androgen-dependent and -independent cell lines". International Journal of Oncology 36, no. 3 (2010): 553-562. https://doi.org/10.3892/ijo_00000529