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Zyflamend inhibits the expression and function of androgen receptor and acts synergistically with bicalutimide to inhibit prostate cancer cell growth
Author(s) -
Yan Jun,
Xie Bingxian,
Capodice Jillian L.,
Katz Aaron E.
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21426
Subject(s) - lncap , androgen receptor , cell growth , prostate cancer , cancer research , biology , signal transduction , flow cytometry , blot , apoptosis , growth inhibition , endocrinology , chemistry , medicine , microbiology and biotechnology , cancer , biochemistry , gene
BACKGROUND Interference of androgen receptor (AR) signaling is a target for prostate cancer (CaP) chemoprevention and treatment. We hypothesize that Zyflamend (ZYF) assert its anti‐cancer effect by disrupting AR signaling. We also hypothesize that it may act synergistically with the anti‐androgen bicalutimde to inhibit CaP cell growth. METHODS Western blotting, ELISA and reporter assays were done to test ZYF on AR signaling. Semi‐quantitative RT‐PCR and AR half‐life were also examined. Potential synergism between ZYF and bicalutimide were tested via cytotoxicity, colony formation assays, flow cytometry, and Western blotting in the human CAP line, LNCaP and 22RV1. RESULTS ZYF reduced AR protein, mRNA and protein stability levels in LNCaPs. ZYF also reduced both full‐length AR protein and truncated AR protein in the 22Rv1 cell line. Nkx3.1 and PSA were also reduced at the mRNA level. PSA promoter activity and secretion were lower after treatment of cells with ZYF. DHT induction of cell proliferation and AR responsiveness revealed reduction of AR, Nkx3.1, and PSA protein were demonstrated with ZYF treatment. Co‐treatment with bicalutimide reducing cell growth, induced apoptosis, and reduced Bcl‐2 and BclxL, caspase‐3 and PARP. Co‐treatment also reduced Nkx3.1 and PSA protein. CONCLUSIONS These data indicate that ZYF suppresses cell growth mediated by AR signaling, and suggests that the co‐treatment with the anti‐androgen bicalutimide and ZYF may be a promising approach for cancer therapy and may demonstrate the mechanism of action of ZYF. Prostate 72:244–252, 2012. © 2011 Wiley Periodicals, Inc.