Search

(A) The hypomethylation and high expression genes in Module 1; (B) the hypomethylation and high expression genes in Module 2; (C) the hypermethylation and low expression genes in Module 1. By comparing these two sets of genes, a number of 162 hypermethylated, low-expressing genes and 190 hypomethylated, highly expressed genes were identified (Figure 2). For microarrays of gene methylation, 1780 overlapping hypermethylated genes (7391 in GSE89852; 5116 in GSE54503) together with 4550 overlapping hypomethylated genes (41,046 in GSE89852; 23,579 in GSE54503) were identified. [Extracted from the article]

Cancer stem cells (CSCs) are considered to play essential roles in the process of origination, proliferation, migration, and invasion of cancer, and their properties are regulated by Wnt/β-catenin pathway. Phenethyl isothiocyanate (PEITC) is a natural product obtained from cruciferous vegetables with anticancer activities. The present study aimed to investigate the inhibitory effect and the underlying mechanisms of PEITC on colorectal CSCs. In this study, we found that PEITC can significantly reduce the size and number of colorectal cancer cell spheroids in serum-free medium. With increasing PEITC concentrations (10-40 μM), the number of spheroids was reduced to about 10% of the control group, and the percentage of CD133+ cells was decreased by about 3-16 folds. PEITC also decreased the expression of CSC markers. Meanwhile, inhibition of proliferation as well as induction of apoptosis of colorectal CSCs was observed after PEITC treatment. Furthermore, through activating Wnt/β-catenin pathway with LiCl, the inhibitory effects of PEITC on colorectal CSCs were diminished. Our data suggested that PEITC can be an effective inhibitor of colorectal CSCs by targeting Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/β-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Jianpi Huayu decoction (JHD) is a traditional Chinese medicinal preparation used to treat a variety of malignant tumors including HCC, although the underlying mechanism remains unknown. Exosomes in the tumor microenvironment mediate intercellular signaling among cancer cells, but precise contributions to hepatocellular carcinoma (HCC) progression are still elusive. In this work, the main objective was to examine the mechanisms underlying anti-tumor effects of JHD and the potential contributions of exosomal signaling. LC-MS/MS was used for quality control of JDH preparation, while nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blotting were used for verification of exosomes. In vitro assays included CCK8, wound healing assay, transwell invasion assay, qRT-PCR and western blotting were performed to investigate the effects of JHD on HCC cells and the molecular mechanism. Furthermore, the effects of JHD on subcutaneous tumor model of nude mice were also determined. JHD inhibited the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of cultured HCC cells. Further, exosomes isolated from EMT-induced HCC cells promoted the migration, invasion and EMT of other cultured HCC cells, while exosomes isolated from EMT-induced HCC cells after JHD treatment had little effect. In addition, JHD reduced the expression of exosomal miR-23a-3p in cultured HCC cells. miR-23a-3p was significantly up-regulated in tumor compared with that in adjacent non-cancerous tissues of patients with HCC. HCC patients with high miR-23a-3p expression had poor overall survival after hepatectomy. Meanwhile, miR-23a-3p enhanced HCC cell proliferation, EMT, and expression of Smad signaling proteins. More importantly, overexpression of miR-23a-3p can reverse the inhibition of EMT and Smad signaling pathway caused by JHD treatment. In vivo assays, treatment with JHD also reduced the growth of HCC-derived tumors in nude mice, reduced the expression of miR-23a-3p in serum exosomes and the level of EMT in tumor cells. the antitumor effects of JHD on HCC are mediated at least in part by inhibition of EMT due to downregulation of exosome-mediated intercellular miR-23a-3p transfer and subsequent blockade of Smad signaling. Disrupting this exosomal miR-23a-3p/Smad signaling pathway may be an effective treatment. [Display omitted] • miR-23a-3p was upregulated in HCC and associated with poor prognosis. • JHD inhibited the EMT of HCC cells both in vitro and in vivo. • The effect of JHD was transmitted through exosomes. • JHD inhibited the expression of exosomal miR-23a-3p. [ABSTRACT FROM AUTHOR]

7′-Hydroxyriccardin C ( 1) and marchantin E ( 2), two macrocyclic bisbibenzyls with a stereogenic center at the ethylene bridge from Chinese liverworts, were investigated stereochemically. Compound 1 was found to be optically active and occurred as a pair of dynamically interchangeable atropisomers at room temperature due to the low barrier of rotation around the biaryl bond, while 2 was a racemic mixture, which was successfully resolved by chiral HPLC into two enantiomers. Their absolute configurations were unequivocally assigned by analysis of temperature-dependent NMR spectra, X-ray crystallographic diffraction, and comparison of experimental and calculated ECD data. [ABSTRACT FROM AUTHOR]

Isoriccardin C (1) and riccardin D (2), isolated from the liverwort Reboulia hemisphaerica, were first characterized to be a mixture of two enantiomeric atropisomers by online chiral high-performance liquid chromatography-circular dichroism (HPLC-CD) analysis. Exemplarily for bisbibenzyls of the diarylether-biphenyl type, the absolute atropisomeric configurations of compunds 1 and 2 were determined by the analysis of their CD data coupled with quantum chemical CD calculations. [ABSTRACT FROM AUTHOR]

Six macrocyclic bis(bibenzyls) were obtained from the Chinese liverwort Ptagiochasm intermedlum L., and their structures were elucidated as pakyonol (1), neomarchantin A (2), isoriccardin C (3), marchantin H (4), riccardin F (5) and riccardin C (6) on the basis of spectroscopic data and comparison with known compounds. Among them, compounds 3-5 were isolated from this liverwort species for the first time. They possessed in vitro antifungal properties against the fluconazole-sensitive and resistant strains of Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 32 to >512 µg mL-1. Furthermore, riccardin C was also demonstrated to act as a fungal resistance modifying agent when its combined effect with fluconazole on three resistant strains of C. albicans was investigated. The synergistic or additive activity of riccardin C caused dramatically reduced MICs of fluconazole by at most 256-fold. [ABSTRACT FROM AUTHOR]

Unfortunately, the online published article has error in Figure 4. The correct Figure 4 is given here. [ABSTRACT FROM AUTHOR]