title: Combination of resveratrol and antiandrogen flutamide has synergistic effect on androgen receptor inhibition in prostate cancer cells.
abstract: Agents targeting the androgen receptor (AR) axis are critical for chemoprevention and treatment of prostate cancer (PCa) at all stages of the disease. Combination molecular targeted therapy may improve overall efficacy. The combination of dietary compound resveratrol with known therapeutic agents, such as the antiandrogen flutamide, may be particularly attractive due to the pharmacological safety of resveratrol.
  
  
  METHODS
  Resveratrol, 5α-dihydrotestosterone and flutamide were used in various experiments using mostly LNCaP cell line. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blots, and luciferase assay were utilized to examine the levels of AR mRNA, and protein and transcriptional activity in response to treatments. Growth proliferation assays were performed in three cell lines (LNCaP, PC3 and Du145).
  
  
  RESULTS
  Treatment of LNCaP cells with resveratrol (1-100 μM) resulted in the inhibition of androgen-promoted growth, inhibition of AR transcriptional activity and decrease in the AR and prostate-specific antigen protein levels through degradation pathways. The combination of resveratrol with flutamide had a synergistic effect on down-regulation of AR.
  
  
  CONCLUSIONS
  Resveratrol works in concert with antiandrogen flutamide to reduce the amount and activity of AR, suggesting new therapeutic strategies for the treatment of PCa.
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, U.S.A.
authors.forename: Li
authors.initials: L
authors.lastname: Kai
authors.forename: Anait S
authors.initials: AS
authors.lastname: Levenson
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005485:Flutamide / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013267:Stilbenes; D013196:Dihydrotestosterone; D005485:Flutamide; D003513:Cycloheximide; D017430:Prostate-Specific Antigen; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; D000077185:Resveratrol