Abstract
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.
Highlights
Zyflamend, a mixture containing extracts of ten herbs, has shown promise in a variety of preclinical cancer models, including prostate cancer
CWR22Rv1 cells were cultured in RPMI 1640 media supplemented with 0.05% fetal bovine serum containing Zyflamend or individual herbal extracts reconstituted in dimethyl sulfoxide (DMSO) for cell proliferation assay, mRNA extraction and protein isolation
To broaden the growing literature on the effects of Zyflamend, we reported that Zyflamend inhibited Histone deacetylase (HDAC) expression (1 and 4) in xenograph models of androgendependent and castrate-resistant prostate cancer (PrC), and wanted to further investigate its impact on the expression of class I and II HDACs and one of their reported targets the tumor suppressor gene p21 [9]
Summary
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. The use of herbs, botanicals and their bioactive components have been shown to be effective in many tumor cell lines in vitro and in vivo by inhibiting cell and tumor growth. The use of herbal extracts in combination potentiates their actions, some synergistically, resulting in Compounds. Percentage (%) Concentration (μg/mL) in 200 μg/mL Zyflamend Ginger Rosemary Turmeric. Chinese goldthread Holy Basil Hu Zhang Barberry Oregano Green tea
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