title: Fenofibrate down-regulates the expressions of androgen receptor (AR) and AR target genes and induces oxidative stress in the prostate cancer cell line LNCaP.
abstract: Fenofibrate, a peroxisome proliferator-androgen receptor-alpha agonist, is widely used in treating different forms of hyperlipidemia and hypercholesterolemia. Recent reports have indicated that fenofibrate exerts anti-proliferative and pro-apoptotic properties. This study aims to investigate the effects of fenofibrate on the prostate cancer (PCa) cell line LNCaP. The effects of fenofibrate on LNCaP cells were evaluated by flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, Western blot analysis, and dual-luciferase reporter assay. Fenofibrate induces cell cycle arrest in G1 phase and apoptosis in LNCaP cells, reduces the expressions of androgen receptor (AR) and AR target genes (prostate-specific antigen and TMPRSS2), and inhibits Akt phosphorylation. Fenofibrate can induce the accumulation of intracellular reactive oxygen species and malondialdehyde, and decrease the activities of total anti-oxidant and superoxide dismutase in LNCaP cells. Fenofibrate exerts an anti-proliferative property by inhibiting the expression of AR and induces apoptosis by causing oxidative stress. Therefore, our data suggest fenofibrate may have beneficial effects in fenofibrate users by preventing prostate cancer growth through inhibition of androgen activation and expression.
authors: State Key Laboratory of Reproductive Medicine, Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Hu
authors: H
authors: Zhao
authors: Chen
authors: C
authors: Zhu
authors: Chao
authors: C
authors: Qin
authors: Tao
authors: T
authors: Tao
authors: Jie
authors: J
authors: Li
authors: Gong
authors: G
authors: Cheng
authors: Pu
authors: P
authors: Li
authors: Qiang
authors: Q
authors: Cao
authors: Xiaoxin
authors: X
authors: Meng
authors: Xiaobing
authors: X
authors: Ju
authors: Pengfei
authors: P
authors: Shao
authors: Lixin
authors: L
authors: Hua
authors: Min
authors: M
authors: Gu
authors: Changjun
authors: C
authors: Yin
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D051057:Proto-Oncogene Proteins c-akt; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen; D011345:Fenofibrate