Thanaset Senawong

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

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.

Effect of end of season water deficit on phenolic compounds in peanut genotypes with different levels of resistance to drought

Terminal drought reduces pod yield and affected the phenolic content of leaves, stems and seed of peanut (Arachis hypogaea L.). The aim of this study was to investigate the effects of end of season water deficit on phenolic content in drought tolerant and sensitive genotypes of peanuts. Five peanut genotypes were planted under two water regimes, field capacity and 1/3 available water. Phenolic content was analyzed in seeds, leaves, and stems. The results revealed that terminal drought decreased phenolic content in seeds of both tolerant and sensitive genotypes. Phenolic content in leaves and stems increased under terminal drought stress in both years. This study provides basic information on changes in phenolic content in several parts of peanut plants when subjected to drought stress. Future studies to define the effect of terminal drought stress on specific phenolic compounds and antioxidant properties in peanut are warranted.

A new cerebroside and the cytotoxic constituents isolated from Xylaria allantoidea SWUF76.

Abstract A new cerebroside, namely allantoside (1), and 10 known compounds (2–11) were isolated from Xylaria allantoidea SWUF76. The structure of compound 1 was determined by comprehensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance (NMR) as well as high-resolution electron ionisation mass spectrometry (HREIMS) and electrospray ionisation mass spectrometry (ESIMS). Compounds 1, 4, 5, 6, 7, 8 and 11 were evaluated for cytotoxic activities against cancer cell lines (Hela, HT29, HCT116 and MCF-7) and normal Vero cell lines by MTT assay. Compounds 6 and 7 exhibited anticancer activity after 24 h of treatment. Compound 7 showed significant cytotoxicity against Hela (IC50 = 2.24 μg/mL), HT29 (IC50 = 2.51 μg/mL), HCT116 (IC50 = 3.50 μg/mL) and MCF-7 (IC50 = 3.77 μg/mL) and Vero (IC50:3.65 μg/mL) cells. Compound 6 showed slight cytotoxicity against all tested cancer cell lines.

Cytotoxic effects of peanut phenolics possessing histone deacetylase inhibitory activity in breast and cervical cancer cell lines

BACKGROUND Epigenetic histone modifications are considered as a promising avenue for cancer preventive and therapeutic strategies. The purpose of this study was to evaluate the antiproliferative and histone deacetylase (HDAC) inhibitory activity of selected peanut phenolics, including p-coumaric acid, ferulic acid, sinapinic acid and resveratrol, in MCF-7 and HeLa cells. METHODS The cytotoxic and HDAC inhibitory activities were assessed by MTT assays, flow cytometric analyses of cell cycle arrest and apoptosis induction, and western blotting. RESULTS The results showed that all four phenolics inhibited proliferation of both MCF-7 and HeLa cells in a dose-dependent manner. Among the phenolics tested, resveratrol was the most effective in inhibiting growth of cancer cells. Treatment with all phenolics resulted in histone H3 hyperacetylation in both cell lines, indicating potential for HDAC inhibition. These phenolics induced apoptosis in both MCF-7 and HeLa cells in a concentration-dependent manner. Moreover, all phenolics induced G0/G1-phase arrest of the cell cycle in MCF-7 cells while p-coumaric and ferulic acids caused S-phase arrest in HeLa cells. Exposure to p-coumaric acid increased p53 and p21 expression but decreased CDK4 levels in both cell types, which could result in the observed G0/G1 arrest. Moreover, inhibition of ERK1/2 phosphorylation by ferulic acid and resveratrol contributed to cell growth inhibition. CONCLUSION Peanut phenolics appear to influence the extent of histone acetylation in MCF-7 and HeLa cells, and this activity modulates multiple pathways that are implicated in cancer prevention.

Anticancer effects of Curcuma C20-dialdehyde against colon and cervical cancer cell lines

BACKGROUND Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. MATERIALS AND METHODS Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. RESULTS Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of 65.4±1.74 μg/ml, 58.4±5.20 μg/ml and 72.0±0.03 μg/ml, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. CONCLUSIONS Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

Chemical constituents and cytotoxic activity from the wood-decaying fungus Xylaria sp. SWUF08-37

Abstract A new cyclic pentapeptide, pentaminolarin (1), and a new cytochalasin, xylochalasin (2), along with thirteen known compounds (3–15) were isolated from the wood-decaying fungus Xylaria sp. SWUF08-37. The absolute configurations of 1 were determined by a combination of Marfey’s method and TDDFT ECD calculation and the absolute configurations of 2 were established by TDDFT ECD calculation. Compound 12 showed moderate cytotoxicity against HeLa (IC50 = 19.60 µg/mL), HT29 (IC50 = 17.31 µg/mL), HCT116 (IC50 = 14.28 µg/mL), MCF-7 (IC50 = 15.38 µg/mL), and Vero (IC50 = 24.97 µg/mL) cell lines by MTT assay. Compounds 1 and 2 showed slight cytotoxicity against all tested cancer cell lines. Graphical Abstract

New histone deacetylase inhibitors from the twigs of Melanorrhoea usitata

Two new compounds, melanorrone (1) and melanorric acid (2), as well as 19 known compounds were isolated and identified from the twigs of Melanorrhoea usitata. Their structures were determined by spectroscopic methods (IR, 1H-NMR, 13C-NMR, 2D-NMR, MS, and ECD). The histone deacetylase (HDAC) inhibitory activities of the obtained compounds were evaluated. Melanorrone (1) along with five known compounds acted as good HDAC inhibitors at 100 μM. Molecular docking experiments of these compounds with representatives of class I (HDAC2 and HDAC8) and class II (HDAC4 and HDAC7) HDAC isoforms displayed potential isoform-selective HDAC inhibitors. Molecular docking data showed consistent results to the in vitro experiments with the high selectivity towards HDAC4 and HDAC8.

Peanut testa extracts possessing histone deacetylase inhibitory activity induce apoptosis in cholangiocarcinoma cells

Previous studies demonstrated that peanut testa extracts (KK4 and ICG15042) containing natural histone deacetylase (HDAC) inhibitors inhibited the growth of several human cancer cell lines via apoptosis induction. The aims of this study were to investigate the anti-proliferative effects and the mechanism(s) responsible for apoptosis induction mediated by these peanut testa extracts in human cholangiocarcinoma cell lines (KKU-M214 and KKU-100). The anti-proliferative effects were assessed by MTT assay. Apoptotic cell death and cell cycle arrest were analyzed by flow cytometry. The caspase activities were studied using colorimetric caspase activity assay and western blot analysis. Our results revealed that KK4 and ICG15042 extracts inhibited cell proliferation of both KKU-M214 and KKU-100 cells in a dose- and time-dependent manner, with IC50 values of 38.28 ± 0.29 (KK4), 43.91 ± 1.94 (ICG15042) μg/mL for KKU-M214 and 78.40 ± 1.74 (KK4), 82.77 ± 0.94 (ICG15042) μg/mL for KKU-100 at 72 h. Apoptosis induction by these peanut testa extracts were observed in both KKU-M214 and KKU-100 cells in a concentration-dependent manner. Moreover, the percentage of cells in the sub-G1 phase was significantly increased in both KKU-M214 and KKU-100 cells. Cell cycle arrest was not observed in other cell cycle phases. Activation of caspases 8 and 3 were apparent integral parts of apoptosis induction in both cells. Both peanut testa extracts also caused down-regulation of p53, p21, Bcl-2 and pERK1/2 protein expression in these cells. These results suggest that peanut testa extracts may be potential anti-cancer agents for cholangiocarcinoma chemoprevention or chemotherapy.

Characterization and localization of Opisthorchis viverrini fructose-1,6-bisphosphate aldolase.

Opisthorchis viverrini (Ov) infection is a long-time public health problem in Thailand that can lead to bile duct cancer, cholangiocarcinoma (CCA). Characterization of the Ov proteins at a molecular level will increase our knowledge of host-parasite interaction that can be applied to new drug, vaccine, or immunodiagnostic development. In this study, an important enzyme in the Ov glycolytic pathway, fructose-1,6-bisphosphate aldolase (FBPA), that had been obtained from a previous study was characterized and immunolocalized. The full-length sequence of OvFBPA gene is 1089bp and encodes 362 amino acids with a predicted molecular weight and isoelectric point of 39.54kDa and 7.61, respectively. Additionally, three OvFBPA isoforms were identified by sequence analysis. The amino acid sequence of OvFBPA-1 characterized in this study shared 98% identity to FBPA isoform 1 of Clonorchis sinensis that was classified based on highly conserved active residues to class-I FBPA. The recombinant OvFBPA-1 protein was expressed as a soluble form in Escherichia coli at 25°C with N-terminal His-tagged fusion protein and the purified OvFBPA-1 protein was used to generate polyclonal antibody in mice. Antibody against rOvFBPA-1 protein was able to detect the native OvFBPA-1 protein in both Ov infected hamster liver section and Ov excretory-secretory (ES) products by immunohistochemistry and western blotting, respectively.

Identification of phenolic compounds from Zingiber offinale and their derivatives as histone deacetylase inhibitors and antioxidants

The aim of this study was to explore histone deacetylase inhibitory and antioxidant activities of natural products from ginger and their semi-synthetic derivatives. Two major phenolic compounds, [6]-gingerol and [6]-shogaol along with three minor phenolic compounds including [6]-gingerdione, 1-dehydro-[6]-gingerdione and [6]-gingerdiol were isolated and tested against histone deacetylase in HeLa nuclear extract. All compounds exhibited histone deacetylase inhibitory activities in micromolar concentrations. 1-dehydro-[6]-gingerdione showed the best inhibition with IC50 value of 42 μM. Thirteen semi-synthetic derivatives of two major natural products were synthesized and tested. The demethylated [6]-shogaol derivative was the best inhibitor among the synthesized compounds with IC50 value of 45 μM. Molecular docking experiments of selected compounds with representatives of class I and class II histone deacetylase isoforms revealed potential isoform-selective histone deacetylase inhibitors. The DPPH assay indicated that most derivatives possessed antioxidant activities superior to their lead compounds. Therefore, the studied compounds could serve as promising leads for safe and selective anticancer agents with histone deacetylase inhibitory and radical scavenging abilities.