TY - JOUR
T1 - Low-dose statin treatment increases prostate cancer aggressiveness
AU - Caro-Maldonado, Alfredo
AU - Camacho, Laura
AU - Zabala-Letona, Amaia
AU - Torrano, Verónica
AU - Fernández-Ruiz, Sonia
AU - Zamacola-Bascaran, Kepa
AU - Arreal, Leire
AU - Valcárcel-Jiménez, Lorea
AU - Martín-Martín, Natalia
AU - Flores, Juana M.
AU - Cortazar, Ana R.
AU - Zúñiga-García, Patricia
AU - Arruabarrena-Aristorena, Amaia
AU - Guillaumond, Fabienne
AU - Cabrera, Diana
AU - Falcón-Perez, Juan M.
AU - Aransay, Ana M.
AU - Gomez-Muñoz, Antonio
AU - Olivan, Mireia
AU - Morote, Juan
AU - Carracedo, Arkaitz
PY - 2018/1/1
Y1 - 2018/1/1
N2 - © 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.
AB - © 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.
KW - Cholesterol
KW - Mouse models
KW - Obesity
KW - Prostate cancer
KW - Statins
U2 - 10.18632/oncotarget.22217
DO - 10.18632/oncotarget.22217
M3 - Article
C2 - 29416709
SN - 1949-2553
VL - 9
SP - 1494
EP - 1504
JO - Oncotarget
JF - Oncotarget
IS - 2
ER -