Dicerandrol C Suppresses Proliferation and Induces Apoptosis of HepG2 and Hela Cancer Cells by Inhibiting Wnt/ß-Catenin Signaling Pathway.

Overwhelming evidence points to an aberrant Wnt/ß-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/ß catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/ß-catenin signaling by inhibiting ß-catenin transcriptional activity and abrogating ß-catenin translocated to the nucleus; down-regulating the transcription level of ß-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-ß, ß-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-ß expression, which indicates that DD-9 stabilized the ß-catenin degradation complex, thereby inducing ß-catenin degradation and inactivation of the Wnt/ß-catenin pathway. The possible interaction between DD-9 and ß-catenin and GSK3-ß protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-ß-mediated crosstalk with the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.

A Review on Metabolites from Onchidium Genus: Chemistry and Bioactivity.

The Onchidium genus (Mollusca, Gastropoda, Pulmonata, Systellommatophora, Onchidiidae family) is used as the important economical shellfish, due to the high nutritional value and medicinal value. Research over the previous decades indicated that Onchidium sp. mainly contains polypropionates, depsipeptides, terpenoids and other chemical components. Many biological activities of Onchidium (e. g., cytotoxic activities against tumor cells, anti-viral and anti-bacterial activities) have been reported. This review reports a total of 60 compounds, synthetic work and biological studies on Onchidium genus, covering the literature from 1978 to date, with a view to providing a reference and helping for the in-depth research of this genus.

Study on physicochemical properties and antioxidant activity of polysaccharides from Desmodesmus armatus.

Physicochemical properties and antioxidant activities of Desmodesmus armatus polysaccharides (DAP) were studied. They were extracted by microwave-assisted constant temperature extraction and purification by DEAE-cellulose 52. Four eluents of water (DAP1), 0.25 mol/L NaCl (DAP2), 0.5 mol/L NaCl (DAP3), and 1.0 mol/L NaCl (DAP4) were collected. Four polysaccharides fractions were analyzed, and they were all composed of mannose, rhamnose, glucuronic acid, galacturonic acid, arabinose, and fucose. Gel Permeation Chromatography (GPC) analysis showed that the four polysaccharides fractions have a uniform molecular weight distribution. Scanning electron microscope showed that DAP1 had a dense structure and a smooth but uneven surface, while DAP2, DAP3, and DAP4 were amorphous solids in sheets. Oxidation in vitro experiments showed that DAP2 and DAP3 had scavenging effects on ABTS, DPPH, and hydroxyl radicals. PRACTICAL APPLICATIONS: In the determination of the antioxidant activity, it was found that the antioxidative activity of the polysaccharide of Desmodesmus armatus measured was significantly stronger than the crude polysaccharide of other microalgae. After the polysaccharide was purified, two polysaccharide fractions (DAP2 and DAP3) of Desmodesmus armatus were found to have strong scavenging ability to ABTS, DPPH, and hydroxyl radicals. They can be regarded as a new type of antioxidant, and the differences in the physicochemical properties between the parts can provide a preliminary explanation for the differences in antioxidant activity. But the connection between them needs further analysis. The Desmodesmus armatus used in the experiment is easy to cultivate and easy to obtain, which greatly increases its applicability. This research opens up new possibilities for the development of antioxidants and provides favorable evidence for the use of Desmodesmus armatus in food and feed.

[Determination of ethylene glycol bis (2-aminoethyl) ether-N,N,N,N-tetraacetic acid in medicine using high performance liquid chromatography].

A method was developed for the determination of ethylene glycol bis(2-aminoethyl) ether-N,N,N,N-tetraacetic acid (EGTA) by high performance liquid chromatography (HPLC). The content of EGTA can be determined by that of EGTA-Cu through the complexation between EGTA and Cu2+. The chromatographic separation was performed on an Ultimate-AQ C18 analytical column (250 mm x 4.6 mm, 5 µm) using the mobile phase of acetonitrile-ion-pairing reagents (with 0.3% tetrabutyl ammonium hydroxide in mass fraction adjusted to pH 6.50 using acetate)-buffered saline (35 mmol/L sodium acetate of pH 6.50) (20:20:60, v/v/v). The chromatographic conditions were as follows: flow rate, 1.50 mL/min; detection wavelength, 245 nm; injection volume, 100 µL; column temperature, 40 °C. Under the conditions, good linear relationships between the mass concentration and the peak area of EGTA were observed in the range of 0.10-15.00 mg/L (R = 0.9998). The limit of detection (LOD, S/N = 3) and limit of quantitation (LOQ, S/N = 10) were determined as 0.05 mg/L and 0.17 mg/L, respectively. The average recoveries were 98.34%-99.03% with the RSDs of 1.08%-3.33% (n = 9). The results showed that the developed method is sensitive, accurate, reproducible and suitable for the analysis of EGTA in medicine.