Low-dose statin treatment increases prostate cancer aggressiveness

Alfredo Caro-Maldonado, Laura Camacho, Amaia Zabala-Letona, Verónica Torrano, Sonia Fernández-Ruiz, Kepa Zamacola-Bascaran, Leire Arreal, Lorea Valcárcel-Jiménez, Natalia Martín-Martín, Juana M. Flores, Ana R. Cortazar, Patricia Zúñiga-García, Amaia Arruabarrena-Aristorena, Fabienne Guillaumond, Diana Cabrera, Juan M. Falcón-Perez, Ana M. Aransay, Antonio Gomez-Muñoz, Mireia Olivan, Juan MoroteArkaitz Carracedo

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

© Caro-Maldonado et al. 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.
Original languageEnglish
Pages (from-to)1494-1504
JournalOncotarget
Volume9
Issue number2
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Cholesterol
  • Mouse models
  • Obesity
  • Prostate cancer
  • Statins

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