Histone deacetylase (HDAC) inhibitory and antiproliferative activities of phenolic-rich extracts derived from the rhizome of Hydnophytum formicarum Jack.: sinapinic acid acts as HDAC inhibitor

Thanaset Senawong,Suporn Nuchadomrong,Suwatchai Misuna,Somprasong Khaopha,Prasan Sawatsitang,Chanokbhorn Phaosiri,Banchob Sripa,Arpa Surapaitoon

doi:10.1186/1472-6882-13-232

Thanaset Senawong, Suporn Nuchadomrong + Show 6 more

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https://doi.org/10.1186/1472-6882-13-232

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Abstract

BackgroundThe rhizome of Hydnophytum formicarum Jack., a medicinal plant known in Thai as Hua-Roi-Roo, has been used in Thai traditional herbal medicine for treatment of cancer. We assessed the ability of its ethanolic and phenolic-rich extracts and its major phenolic compound, sinapinic acid, possessing histone deacetylase (HDAC) inhibitory activity to inhibit proliferation of 5 human cancer cell lines.MethodsHeLa cells were used to study HDAC inhibitory activity of the extracts, sinapinic acid, and a well-known HDAC inhibitor sodium butyrate. Five human cancer cell lines and one non-cancer cell line were used to study antiproliferative activities of the plant extracts, sinapinic acid and sodium butyrate, comparatively.ResultsResults indicated that ethanolic and phenolic-rich extracts of H. formicarum Jack. rhizome possessed both antiproliferative activity and HDAC inhibitory activity in HeLa cells. Sinapinic acid, despite its lower HDAC inhibitory activity than the well-known HDAC inhibitor sodium butyrate, inhibited the growth of HeLa and HT29 cells more effectively than sodium butyrate. However, sinapinic acid inhibited the growth of HCT116 and Jurkat cells less effectively than sodium butyrate. The non-cancer cell line (Vero cells) and breast cancer cell line (MCF-7 cells) appeared to be resistant to both sinapinic acid and sodium butyrate. The growth inhibitory effects of the ethanolic and phenolic-rich extracts and sinapinic acid in HeLa cells were mediated by induction of apoptosis.ConclusionsThe results of this study support the efficacy of H. formicarum Jack. rhizome ethanolic and phenolic-rich extracts for the treatment of cervical cancer, colon cancer, and T- cell leukemia in an alternative medicine. Further studies of other active ingredients from this plant are needed.

Highlights

The rhizome of Hydnophytum formicarum Jack., a medicinal plant known in Thai as Hua-Roi-Roo, has been used in Thai traditional herbal medicine for treatment of cancer
In vitro histone deacetylase (HDAC) inhibitory activity of the extracts from H. formicarum Jack. rhizome The effect of various polarity extracts including fractionated solvent extracts from hexane soluble fraction, ethyl acetate soluble fraction, methanol soluble fraction and ethanolic crude extract on in vitro HDAC activity was examined by using HeLa nuclear extract as a source of the HDAC enzymes
The results in this report demonstrated that ethanolic crude extract and phenolic-rich extract from H. formicarum Jack. rhizome inhibited HDAC activity both in vitro and in the cells

Summary

Introduction

The rhizome of Hydnophytum formicarum Jack., a medicinal plant known in Thai as Hua-Roi-Roo, has been used in Thai traditional herbal medicine for treatment of cancer. HDAC inhibitors that act on zinc-dependent HDAC isozymes have three structural characteristics: a zinc-binding moiety, an opposite capping group, and a straight chain alkyl, vinyl or aryl linker connecting the zinc-binding moiety and the capping group [9] Based on their chemical structures, HDAC inhibitors can be classified into four subtypes: (1) short chain fatty acid; (2) hydroxamic acids; (3) benzamides; and (4) cyclic peptides [13]. Their mechanisms of action are largely unknown, major consequences usually observed upon treatment with HDAC inhibitors include growth arrest, apoptosis, and inhibition of angiogenesis [9]. HDAC inhibitor treatments resulted in cancer cell apoptosis due to a shift in the balance of pro- and antiapoptotic genes toward apoptosis [15]

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