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

Jay Whelan⁴  John P Biggerstaff²  Steven Minkin²  Michael F McEntee³  Seung Joon Baek³  Guoxun Chen¹  Yi Zhao¹  E-Chu Huang¹ 

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

[2]Center for Environmental Biotechnology, University of Tennessee, Knoxville, TN 37996, USA

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

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

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

Others  :  1220253
DOI  :  10.1186/1472-6882-14-68

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

【 摘 要 】

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.

【 授权许可】

   
2014 Huang et al.; licensee BioMed Central Ltd.

【 图 表 】

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