title: Zyflamend reduces the expression of androgen receptor in a model of castrate-resistant prostate cancer.
abstract: Prostate cancer is the most commonly diagnosed solid malignancy, and tumor cells eventually transform to castrate resistance through multiple pathways including activation of the androgen receptor via insulin-like growth factor receptor (IGF-1R) signaling involving phospho-AKT (pAKT). In this study, a mixture of herbal extracts, Zyflamend®, was used as a treatment in a model of castrate-resistant prostate cancer using CWR22Rv1 cells. Zyflamend reduced androgen receptor and IGF-1R expression along with a reduction of IGF-1-mediated proliferation of CWR22Rv1 cells. IGF-1 induced downstream AKT phosphorylation; however, the induction of pAKT was not associated with androgen receptor expression. Further, constitutively active form of AKT had no effect on nuclear expression of androgen receptor, indicating that upregulation of pAKT did not promote androgen receptor expression or nuclear translocation in castrate-resistant CWR22Rv1 cells. Conversely, Zyflamend reduced androgen receptor expression following IGF-1 stimulation and in cells overexpressing pAKT. These results demonstrated that Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen receptor expression and its nuclear localization, but these effects were not dependent upon phosphatidylinositol 3-kinase/pAKT signaling. In conclusion, Zyflamend decreased cell proliferation and inhibited IGF-1R and androgen receptor expression in a phosphatidylinositol 3-kinase/pAKT independent manner.
authors.affiliation: Department of Nutrition, University of Tennessee, Knoxville, Tennessee 37996-1920, USA.
authors.forename: E-Chu
authors.initials: EC
authors.lastname: Huang
authors.forename: Guoxun
authors.initials: G
authors.lastname: Chen
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
authors.forename: Michael F
authors.initials: MF
authors.lastname: McEntee
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Collier
authors.forename: Steven
authors.initials: S
authors.lastname: Minkin
authors.forename: John
authors.initials: J
authors.lastname: Biggerstaff
authors.forename: Jay
authors.initials: J
authors.lastname: Whelan
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: C410798:AR protein, human; D010936:Plant Extracts; D011944:Receptors, Androgen; C519312:Zyflamend; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt