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Open Access Research article

Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells

E-Chu Huang1, Yi Zhao1, Guoxun Chen1, Seung Joon Baek2, Michael F McEntee2, Steven Minkin3, John P Biggerstaff3 and Jay Whelan14*

Author Affiliations

1 Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, Room 229 Jessie Harris Building, Knoxville, TN 37996, USA

2 Department of Biomedical and Diagnostic Sciences, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA

3 Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN 37996, USA

4 Tennessee Agricultural Experiment Station, University of Tennessee, Knoxville, TN 37996, USA

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BMC Complementary and Alternative Medicine 2014, 14:68  doi:10.1186/1472-6882-14-68

Published: 21 February 2014

Abstract

Background

Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer. The current experiments were designed to investigate the effects of Zyflamend on the expression of class I and II histone deacetylases, a family of enzymes known to be over expressed in a variety of cancers.

Methods

CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and II histone deacetylases, along with their downstream target the tumor suppressor gene p21, was investigated. Involvement of p21 was confirmed with siRNA knockdown and over expression experiments.

Results

Zyflamend down-regulated the expression of all class I and II histone deacetylases where Chinese goldthread and baikal skullcap (two of its components) appear to be primarily responsible for these results. In addition, Zyflamend up regulated the histone acetyl transferase complex CBP/p300, potentially contributing to the increase in histone 3 acetylation. Expression of the tumor suppressor gene p21, a known downstream target of histone deacetylases and CBP/p300, was increased by Zyflamend treatment and the effect on p21 was, in part, mediated through Erk1/2. Knockdown of p21 with siRNA technology attenuated Zyflamend-induced growth inhibition. Over expression of p21 inhibited cell growth and concomitant treatment with Zyflamend enhanced this effect.

Conclusions

Our results suggest that the extracts of this polyherbal combination increase histone 3 acetylation, inhibit the expression of class I and class II histone deacetylases, increase the activation of CBP/p300 and inhibit cell proliferation, in part, by up regulating p21 expression.

Keywords:
Zyflamend; p21; Epigenetic; Prostate cancer; CWR22Rv1; Histone deacetylase; HDAC; Histone acetyltransferase; CBP/p300; Herbs; Castrate-resistant