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

BMC Complementary and Alternative Medicine

Research Article

John P Biggerstaff¹  Steven Minkin¹  Michael F McEntee²  Seung Joon Baek²  E-Chu Huang³  Guoxun Chen³  Yi Zhao³  Jay Whelan⁴ 

[1] Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA;Department of Biomedical and Diagnostic Sciences, University of Tennessee, 2407 River Drive, 37996, Knoxville, TN, USA;Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, Room 229 Jessie Harris Building, 37996, Knoxville, TN, USA;Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, Room 229 Jessie Harris Building, 37996, Knoxville, TN, USA;Tennessee Agricultural Experiment Station, University of Tennessee, 37996, Knoxville, TN, USA;

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

DOI  :  10.1186/1472-6882-14-68

 received in 2013-07-16, accepted in 2014-02-13,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundZyflamend, 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.MethodsCWR22Rv1 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.ResultsZyflamend 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Huang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.