Beyond the Abstract - Lovastatin causes diminished PSA secretion by inhibiting AR expression and function in LNCaP prostate cancer cells, by Lin Yang, PhD

BERKELEY, CA (UroToday.com) - Statins are commonly used by patients with high blood cholesterol.

Additionally, there is increasing evidence that statins also have tumor-inhibiting properties. More and more data emerge from clinical trials suggesting that statin users may have a lower risk of developing prostate cancer than non statin-users. A recently published clinical trial, for instance, reports that the use of statins is linked with a significantly reduced risk for developing total and high-grade prostate cancer.1 Most of these clinical studies were retrospective and showed a significant reduction of blood PSA levels in men who regularly take statins.

In a recently published in vitro study, we have shown that lovastatin has a strong influence on the androgen/androgen receptor (AR) signaling cascade. In particular, we have shown that therapeutic concentrations of lovastatin significantly impair androgen activation and expression, thereby resulting in diminished PSA levels.2 Similarly, Yokomizo et al. showed that mevastatin and simvastatin are able to reduce prostate cancer cell proliferation by decreasing AR protein levels.3 These experimental findings indicate that reduced blood PSA levels in statin users are likely caused by impaired androgen/AR signaling and may therefore have a beneficial effect on restricting prostate cancer growth and development.

Nevertheless, we also must take into account that statin-induced inhibition of the androgen/AR signaling cascade is one, but not the only possible mechanism of inhibiting prostate cancer cell growth. Experimental data revealed that statins are also able to inhibit AR negative prostate cancer cell lines and exert pleiotropic effects on inflammation or other signaling transduction pathways such as PI3K/Akt.

Another important issue is that statin-induced reduction of PSA may not always be beneficial, especially in the case of tumor diagnosis. In fact, Ritch et al. recently postulated that the use of statins may be a risk for patients with prostate cancer following radical prostatectomy. The authors concluded from their findings that the reduction of preoperative PSA levels could delay diagnosis and/or mask aggressive disease.4 These findings were supported by another report on a population-based case-control study which concluded that statins are not beneficial, but by contrast may increase the risk of prostate cancer.5 Perspective clinical studies to evaluate the effects of statins on cancer prevention and also more basic studies are required to elucidate the exact mechanisms and function of statins in prostate cancer.

 

References:

  1. Farwell WR, D'Avolio LW, Scranton RE, Lawler EV, Gaziano JM. Statins and prostate cancer diagnosis and grade in a veterans population. J Natl Cancer Inst. 2011 Jun 8;103(11):885-92
  2. Yang L, Egger M, Plattner R, Klocker H, Eder IE. Lovastatin causes diminished PSA secretion by inhibiting AR expression and function in LNCaP prostate cancer cells. Urology. 2011 Jun;77(6):1508.e1-7
  3. Yokomizo A, Shiota M, Kashiwagi E, Kuroiwa K, Tatsugami K, Inokuchi J, Takeuchi A, Naito S. Statins reduce the androgen sensitivity and cell proliferation by decreasing the androgen receptor protein in prostate cancer cells. Prostate 71(3):298-304, 2011
  4. Ritch CR, Hruby G, Badani KK, Benson MC, McKiernan JM. Effect of statin use on biochemical outcome following radical prostatectomy, BJU Int. 2011 Mar 31. [Epub ahead of print]
  5. Chang CC, Ho SC, Chiu HF, Yang CY. Statins increase the risk of prostate cancer: A population-based case-control study. Prostate. 2011 Apr 7. [Epub ahead of print]

 

Written by:
Lin Yang, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

 

Lovastatin causes diminished PSA secretion by inhibiting AR expression and function in LNCaP prostate cancer cells - Abstract

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