Low-dose statin treatment increases prostate cancer aggressiveness - Aix-Marseille Université Access content directly
Journal Articles Oncotarget Year : 2018

Low-dose statin treatment increases prostate cancer aggressiveness

Alfredo Caro-Maldonado
  • Function : Author
Laura Camacho
  • Function : Author
Amaia Zabala-Letona
  • Function : Author
Veronica Torrano
  • Function : Author
Sonia Fernandez-Ruiz
  • Function : Author
Kepa Zamacola-Bascaran
  • Function : Author
Leire Arreal
  • Function : Author
Lorea Valcarcel-Jimenez
  • Function : Author
Natalia Martin-Martin
  • Function : Author
Juana M. Flores
  • Function : Author
Ana R. Cortazar
  • Function : Author
Patricia Zuniga-Garcia
  • Function : Author
Amaia Arruabarrena-Aristorena
  • Function : Author
Diana Cabrera
  • Function : Author
Juan M. Falcon-Perez
  • Function : Author
Ana M. Aransay
  • Function : Author
Antonio Gomez-Munoz
  • Function : Author
Mireia Olivan
  • Function : Author
Juan Morote
  • Function : Author
Arkaitz Carracedo
  • Function : Author

Abstract

Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer.

Dates and versions

hal-02143588 , version 1 (29-05-2019)

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Alfredo Caro-Maldonado, Laura Camacho, Amaia Zabala-Letona, Veronica Torrano, Sonia Fernandez-Ruiz, et al.. Low-dose statin treatment increases prostate cancer aggressiveness. Oncotarget, 2018, 9 (2), pp.1494-1504. ⟨10.18632/oncotarget.22217⟩. ⟨hal-02143588⟩

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