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Updated: May 29, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Zyflamend reduces the expression of androgen receptor in a model of castrate-resistant prostate cancer
E-Chu Huang1, Guoxun Chen, Seung Joon Baek
1Department of Nutrition, University of Tennessee, Knoxville, Tennessee 37996-1920, USA.
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.
Insights
Zyflamend, a herbal extract, inhibits prostate cancer growth by reducing androgen receptor and IGF-1R expression. These effects on castrate-resistant prostate cancer cells occur independently of the AKT signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Herbal Medicine
Background:
- Prostate cancer commonly becomes castrate-resistant through androgen receptor (AR) activation, often involving insulin-like growth factor receptor (IGF-1R) and phospho-AKT (pAKT) signaling.
- Understanding resistance mechanisms is crucial for developing effective treatments for advanced prostate cancer.
Purpose of the Study:
- To investigate the efficacy of Zyflamend, a herbal extract mixture, in a castrate-resistant prostate cancer (CRPC) model.
- To elucidate the molecular mechanisms underlying Zyflamend's action, particularly its interaction with AR, IGF-1R, and AKT signaling.
Main Methods:
- Utilized CWR22Rv1 cells, a model for castrate-resistant prostate cancer.
- Administered Zyflamend and assessed its impact on AR, IGF-1R, and pAKT expression and localization.
- Investigated the role of AKT signaling in AR regulation and the effect of Zyflamend in this context.
Main Results:
- Zyflamend reduced AR and IGF-1R expression and inhibited IGF-1-mediated proliferation in CWR22Rv1 cells.
- While IGF-1 stimulated AKT phosphorylation (pAKT), this was not linked to AR expression. Constitutively active AKT did not affect AR nuclear translocation.
- Zyflamend decreased AR expression even when stimulated by IGF-1 or in cells overexpressing pAKT, independent of PI3K/AKT signaling.
Conclusions:
- Zyflamend effectively inhibits cell proliferation and reduces IGF-1R and AR expression in CRPC models.
- The anti-cancer effects of Zyflamend in this model are mediated through pathways independent of the PI3K/AKT signaling cascade.
- Zyflamend represents a potential therapeutic agent for castrate-resistant prostate cancer, acting via novel mechanisms.
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