Tumor Cell Lines HepG2 Research Articles

Synthesis of Gold Nanoparticles (AuNPs) Using Ricinus communis Leaf Ethanol Extract, Their Characterization, and Biological Applications.

The purpose of this study was to explore the collective biological properties of Ricinus communis ethanol leaf extract (RcExt) and extract-fabricated gold nanoparticles (RcExt-AuNPs). AuNPs were synthesized using RcExt. Fingerprint data of the biochemicals putatively found in RcExt were obtained using gas chromatography–mass spectrometry (GC-MS/MS) and high-performance liquid chromatography/ultraviolet-visible (HPLC/UV-VIS) analyses. RcExt-AuNPs were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), and Fourier- transform infrared radiation (FTIR) spectroscopy. Cytotoxic activity on the Hela and HepG2 tumor cell lines was tested through cell viability, antimicrobial activity against bacterial and fungal pathogens through a well diffusion assay, hemolytic activity on red blood cells through absorbance reading, and stimulatory/inhibitory effects on splenic cells by cell viability. AuNPs of 200 nm size were synthesized. GC-MS/MS analysis revealed 12 peaks and HPLC/UV-VIS analysis resulted in 18, 13, and five peaks at the wavelengths of 220, 254, and 300 nm, respectively. Cytotoxicity screening revealed that RcExt had stimulatory effects (6.08%) on Hela cells and an inhibitory effect (−28.33%) on HepG2 cells, whereas RcExt-AuNPs showed inhibitory effects (−58.64% and −42.74%) on Hela and HepG2 cells, respectively. Antimicrobial activity of RcExt-AuNPs against tested pathogens was significantly higher (average diameters of inhibition zones were higher (ranging from 9.33 mm to 16.33 mm)) than those of RcExt (ranging from 6.00 mm to 7.33 mm). RcExt and RcExt-AuNPs showed 4.15% and 100% lytic effects, respectively. Inhibitory effects on splenic cells for RcExt-AuNPs were observed to be significantly higher (−30.56% to −72.62%) than those of RcExt (−41.55% to −62.25%) between concentrations of 25 to 200 µg/mL. RcExt-AuNPs were inhibitory against HepG2 and Hela cells, while RcExt inhibited HepG2 but stimulated Hela cells. RcExt-AuNPs showed comparatively more antimicrobial activity. RcExt was safe while RcExt-AuNPs harmful to red blood cells (RBCs). RcExt and RcExt-AuNPs showed inhibitory effects on splenic cells irrespective of dose.

Further terpenoids from Euphorbia tirucalli

The phytochemical investigation of Euphorbia tirucalli L. (Euphorbiaceae) yielded four new compounds, including a rare cadalene-type sesquiterpene (tirucadalenone), two tirucallane triterpenoids, euphorol L and euphorol M, with the latter being described as an epimeric mixture, and a euphane triterpene, namely, euphorol N, together with 7 known compounds. Their structures and absolute configurations were elucidated from analysis of 1D (1H, J-modulated 13C) and 2D NMR (HSQC, HMBC and NOESY), high-resolution mass spectrometry (HRESIMS), optical rotation, and GIAO NMR shift calculation followed by CP3 analysis, along with comparison with literature reports. All these compounds were tested for cytotoxicity against K562, MCF-7 and/or and HepG2 tumor cell lines. Only tirucadalenone displayed a mild cytotoxic activity.

Triterpenoids and triterpenoid saponins from Dipsacus asper and their cytotoxic and antibacterial activities

Phytochemical investigation of the ethyl acetate soluble part, generated from the ethanol extract of the roots of Dipsacus asper, led to the separation and identification of three undescribed triterpenoids including one arborinane type, one ursane type and one oleanane type, two unreported oleanane type triterpenoid arabinoglycosides, and 18 known analogues. Structures of these compounds were determined by comprehensive spectroscopic analyses, with the absolute configurations of 25-acetoxy-28-dehydroxyrubiarbonone E and 2α,3β-dihydroxy-23-norurs-4(24),11,13(18)-trien-28-oic acid being established by evaluation of their experimental and calculated ECD spectra. 25-Acetoxy-28-dehydroxyrubiarbonone E features an oxygenated C-25 that is the first case among arborinane type triterpenoids, while 2α,3β,24-trihydroxy-23-norurs-12-en-28-oic acid incorporates a sp3 C-24 that is a rare structural feature of 23-norursane type triterpenoids. Of these isolates, 2′,4′-O-diacetyl-3-O-α-l-arabinopyranosyl-23-hydroxyolea-12-en-28-oic acid and hederagonic acid exhibited moderate antibacterial activity against Staphylococcus aureus with IC50 values of 12.3 and 10.3 μM, respectively, while those with either a feruloyloxy group or an arabinosyl moiety at C-3 displayed potent cytotoxic activities against four tumor cell lines A549, H157, HepG2 and MCF-7.

Perisomalien A, a new cytotoxic scalarane sesterterpene from the fruits of Periploca somaliensis

The CHCl3 fraction of MeOH extract of Periploca somaliensis (family Asclepiadaceae) fruits afforded a new scalarane sesterterpene, namely perisomalien A (1), along with lupeol acetate (2), β-amyrin (3), cycloart-23Z-ene-3β,25-diol (4), and β-sitosterol-3-O-β-D-glucopyranoside (5). Their chemical structures were established by various spectroscopic analyses, in addition to comparison with the formerly reported data. Moreover, the cytotoxic activity of these metabolites was assessed towards MCF-7, HepG2, and HCT-116 tumour cell lines using sulforhodamine B (SRB) assay. Compound 4 showed the most potent cytotoxic profile with IC50 9.0 µM towards MCF-7, compared to doxorubicin (IC50 0.18 µM). Also, 1 and 4 possessed the most potent effect towards HepG2 with IC50s 26.7 and 25.9 μM, respectively. In addition, all tested compounds showed cytotoxic effects with IC50 values ranging from 19.9 to 39.3 µM against HCT-116.

Chemical constituents of the trunks and roots of Thuja sutchuenensis

Five new compounds including two stilbenes, designated thujasutchins A (1) and B (2), two phenolic compounds namely thujasutchins C (3) and D (4), as well as one sesquiterpene thujasutchin E (5), were isolated from the 95% ethanolic extract from the trunks and roots of Thuja sutchuenensis. Their structures were determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, 1H and 13C NMR (COSY, HSQC, HMBC). Moreover, compounds 1, 3–5 were evaluated for in vitro cytotoxic activities against SF-268, MCF-7, HepG-2, and A549 tumor cell lines.

Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity.

Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards ‘normal’ liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.

Cytotoxic triquinane-type sesquiterpenoids from the endophytic fungus Cerrena sp. A593

The culture broth of Cerrena sp. A593, which was isolated from Pogostemon cablin, showed potent cytotoxicity against several human tumor cell lines. The following chemical study resulted in the isolation of two new triquinane-type sesquiterpenoids, named cerrenins D (1) and E (2), along with two known compounds plerocybellone A (3) and chloriolin B (4). Their structures were fully assigned with the aid of extensive spectroscopic analysis (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, HRESIMS, and IR) and data from the literature. Moreover, cytotoxic activity in vitro of compounds 1–4 were evaluated against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound 1 exhibited weak growth inhibitory activity against all the four tumor cell lines with IC50 values of 41.01, 14.43, 29.67, 44.32 μM.

Antiproliferative and apoptogenic effects of myosmine on erythroleukemia and hepatocellular carcinoma cells

Myosmine, 3-(1-pyrroline-2-yl) pyridine is a minor tobacco alkaloid that has also been found in various widely used foods. Recently, this phytochemical has been gaining an increasing interest as a potential risk factor for the development of oesophageal adenocarcinoma. This study aimed to examine the effects of myosmine on the cell viability and proliferative activity of erythroleukemia and hepatocellular carcinoma cells and to obtain additional information about the mechanisms underlying its cytotoxic activity. The in vitro cytotoxic effect of myosmine on the HepG2 and MEL tumour cell lines was assessed by MTT dye reduction and trypan blue dye exclusion assays. The alterations in the tumour cell morphology induced by myosmine were analysed by fluorescent microscopy after staining with acridine orange (AO)/ethidium bromide (EtBr) and 4′,6-diamidine-2′-phenylindole dihydrochloride (DAPI). Annexin V-FITC/propidium iodide (PI) staining was used to assess the apoptosis-inducing ability of myosmine. The modulating action of antioxidant treatment on myosmine-induced cytotoxicity against the HepG2 tumour cell line was also examined. The cell viability tests indicated that myosmine induced a significant dose-dependent reduction of the viability and proliferative activity of both tumour cell lines. Fluorescent microscopy studies revealed marked alterations in the morphology of myosmine-treated tumour cells with signs of cell cycle arrest and apoptosis. The results of the simultaneous treatment with myosmine and vitamin C showed modulating activity of vitamin C on the cytotoxic effect of myosmine with concentration- and time-dependent variations. The presented results could contribute to the assessment of the potential health risks associated with the dietary myosmine exposure. Abbreviations AO: acridine orange; DAPI: 4‘,6-diamidine-2‘-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle medium; DMSO: dimethyl sulfoxide; EtBr: ethidium bromide; FITC: fluorescein isothiocyanate; GERD: gastroesophageal reflux disease; MEL: murine erythroleukemia; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NNN: N'-nitrosonornicotine; PBS: phosphate buffered saline; PI: propidium iodide

Taxol production by an endophytic fungus, Cladosporium and #8206; cladosporioides isolated from Catheranthus roseus

Different endopthytic fungi isolated from Catheranthus roseus were tested for their ability to produce Taxol. Taxol extracted from fermentation culture of the isolated fungus Cladosporium‎ cladosporioides was identified by UV, TLC, mass spectroscopy and HPLC. The isolated strain was identified as Cladosporium‎ cladosporioides based on morphological characteristics and the analysis of the 18S rDNA sequence. HPLC quantification of fungal Taxol showed that Cladosporium‎ cladosporioides was capable of producing 700µg/l of Taxol on potato dextrose broth. The optimum culture conditions for Taxol production by the isolated Cladosporium‎ cladosporioides were tested on M1D medium after 10 days of incubation at 25 °C, pH 5.5 in the presence of sucrose and ammonium tartrate as carbon and nitrogen sources respectively. Also different concentrations of benzoic acid, 4-hydroxy benzoic acid, vanadyl sulphate, serinol and salicylic acid were evaluated for their inducing activity on Taxol production by the isolated endophytic fungus. This study offers important information and a new source for the production of the important anticancer drug Taxol by endophytic fungus fermentation. The antitumor activity of fungal Taxol was tested against human tumor cell line HepG-2 (liver carcinoma) using in vitro clonogenic assays.

New cytotoxic bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch

Three new bufadienolides 14β, 16β-dihydroxy-3β-[β-D-glucopyranosyl-(1→6)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (1), 14β-hydroxy-3β-[β-D-glucopyranosyl-(1→4)-(β-D-glucopyranosyl)oxy]-5α-bufa-20, 22-dienolide (2) and hellebrigenin-3-O-β-D-glucosyl-(1→4)-β-D-glucoside (3), together with eight known bufadienolides (4–11) were isolated from the roots and rhizomes of Helleborus thibetanus. Their structures were elucidated by extensive spectroscopic methods and acid hydrolysis. Compounds 1–7 were evaluated for their cytotoxic activity against HCT116, A549 and HepG2 tumor cell lines. Compound 1 exhibited moderate cytotoxicity against HepG2 cells with IC50 value of 15.1 ± 1.72 μM. Compounds 5 and 6 exhibited moderate cytotoxicity against HCT116 cells with IC50 values of 15.12 ± 0.58 μM and 13.17 ± 2.34 μM, respectively.

A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus Emericellopsis alkalina.

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

Three New Complexes of Theophylline Drug with Sc(III), Nb(V), and W(VI) Ions: Spectroscopic, Thermal Stability, and Antimicrobial Studies

Herein, three newly synthesized theophylline (TPE) complexes with transition metal ions (Sc3+, Nb5+ and W6+) are characterized by FT-IR and UV-Vis spectra, magnetic and thermogravimetric analysis, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and transmittance electron microscopy (TEM). FT-IR spectra confirm that the metal ions coordinate to TPE chelate as a mono-dentate ligand via nitrogen atom N7 of the deprotonated NH group. Theophylline complexes are formed in 1 : 2 (metal: ligand) stoichiometry. According to TGA curves the complexes do not contain crystallization water outside the binding spheres. The accumulated data indicate the octahedral geometry for Sc(III) and W(VI) complexes. The Nb(V) complex is four coordinated. Sc(III) And W(VI) complexes in DMSO demonstrate non-electrolytic nature, and Nb(V) complex acts as an electrolyte. The TPE complexes are tested in vitro against bacteria (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus) and fungi (Aspergillus flavus and Candida albicans). The complexes exhibit high antimicrobial activity. The in vitro anticancer activity of Sc(III) complex is screened against the human hepato cellular carcinoma (HepG-2) tumor cell line.

Metal-Drug Interactions: Synthesis and Spectroscopic Characteristics, Surface Morphology, and Pharmacological Activity of Ephedrine–HCl Complexes with Mo(V), Nb(V), Ga(III), and Ge(IV)

Four new Mo(V), Nb(V), Ga(III), and Ge(IV) ephedrine complexes, [Mo(Eph)2(Cl)4].Cl, [Nb(Eph)2(Cl)3], [Ga(Eph)2(Cl)3], and [Ge(Eph)2(Cl)2] are synthesized and characterized. Composition and coordination behavior of ephedrine drug towards Mo(V), Nb(V), Ga(III), and Ge(IV) ions are deduced from microanalysis, IR spectra, molar conductance, magnetic and thermal analysis data. These support coordination of the eph ligand in its neutral state. Ephedrine has two powerful chelating sites, OH and NH, that determine its uni- or bidentate mode of action. IR spectra indicate that Mo(V) and Ga(III) coordinate to ephedrine via nitrogen atom of the NH group as a unidentate chelator with six and five coordination geometry, respectively. On the other hand, Eph ligand behaves as a monoanionic bidentate no chelating agent via the NH and deprotonated OH groups in Nb(V) and Ge(IV) complexes. Mo(V) complex demonstrates electrolytic properties, the other complexes are non-electrolytes in DMSO solutions. TG/DTG analysis makes it possible to calculate the number of solvent molecules in and outside the coordination sphere, and estimate stability of the synthesized complexes. The Eph complexes are screened in vitro for antibacterial (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus) and antifungal (Aspergillus flavus and Candida albicans) activities. Anti-cancer action of the Mo(V) and Ga(III) complexes is assessed against the human hepato cellular carcinoma (HepG-2) tumor cell line (IC50 >1000 μg/mL).

Lithocarpinols A and B, a pair of diastereomeric antineoplastic tenellone derivatives from the deep-sea derived fungus Phomopsis lithocarpus FS508

Lithocarpinols A (1) and B (2), a pair of tenellone diastereoisomers with novel fused skeleton were isolated from the deep-sea derived fungus Phomopsis lithocarpus FS508. Their structures were elucidated by comprehensive spectroscopic analyses, X-ray diffraction and quantum molecular calculation. Their plausible biogenetic pathway featured an intriguing carbonyl-ene cyclization. Lithocarpinol A exhibited moderate inhibitory effect against HepG-2 and A549 tumor cell lines with IC50 values of 9.4 μmol/L and 10.9 μmol/L, respectively.

Unraveling the structural and molecular properties of 34-residue levans with various branching degrees by replica exchange molecular dynamics simulations.

Levan has various potential applications in the pharmaceutical and food industries, such as cholesterol-lowering agents and prebiotics, due to its beneficial properties, which depend on its length and branching degree. A previous study also found that the branching degree of levan affected anti-tumor activities against SNU-1 and HepG2 tumor cell lines. Despite its promising potential, the properties of levans with different branching degrees are not well understood at the molecular level. In two models of the generalized Born implicit solvent (GBHCT and GBOBC1), we employed replica-exchange molecular dynamics simulations to explore conformational spaces of 34-residue levans (L34) with branching degrees of zero (LFO34B0), one (LFO34B1), three (LFO34B3) and five (LFO34B5), as well as to elucidate their structural and molecular properties. To ensure a fair comparison of the effects of branching degree on these properties, we focused on analyzing the properties of the central 21-residue of the main chains of all systems. Our results show that all major representative conformations tend to form helix-like structures with kinks, where two-kink helix-like structures have the highest population. As branching degree increases, the population of helix-like structures with zero or one kink tends to increase slightly. As the number of kinks in the structures with the same branching degree increases, the average values of the lengths and angles among centers of masses of three consecutive turns of residue i, i+3, and i+6 tended to decrease. Due to its highest occurring frequencies, the O6 (i)—H3O (i+1) hydrogen bond could be important for helix-like structure formation. Moreover, hydrogen bonds forming among the branching residue (br), branching position (bp) and other residues of L34B1, L34B3 and L34B5 were identified. The O1(bp)—H3O(br), O1(br)—H3O(br) and O5(br)—H1O(br) hydrogen bonds were found in the first-, second- and third-highest occurrence frequencies, respectively. Our study provides novel and important insights into conformational spaces and the structural and molecular properties of 34-residue levans with various branching degrees, which tend to form helix-like structures with kinks.

Synthesis, structure interpretation, antimicrobial and anticancer studies of tranexamic acid complexes towards Ga(III), W(VI), Y(III) and Si(IV) metal ions

A new four tranexamic acid (TXA) complexes of some transition metal ions yttrium(III), tungsten(VI), and non-transition metal ion gallium(III) and silicon(IV) have been prepared. The TXA synthesized complexes have been characterized by molar conductance, magnetic susceptibility, infrared, electronic spectral, 1HNMR, thermal analyses, X-ray diffraction patterns, scanning and transmittance electron microscopies, and elemental microanalysis (C, H, N, and Cl). The study shows that these complexes have octahedral geometry with the formulas [Ga(TXA)2(Cl)3(H2O)], [Si(TXA)2(Cl)4], [W(TXA)2(Cl)2]·Cl2 and [Y(TXA)2(Cl)(H2O)]·4H2O. Tranexamic acid complexes were formed in 1:2 (metal: ligand) stoichiometry. Based on the reported results, it may be concluded that in case of transition metal ions (tungsten(VI) and yttrium(III)) the deprotonated ligand (TXA) to tranexamate ion coordinated to metal –COO carboxylate ions as bidentate ligand through the oxygen atom of the carboxylate group and the nitrogen atom of the amino group –NH2, where the TXA ligand coordinated as a monodentate through the nitrogen atom of –NH2 group in case of non-transition metal ions. The metal complexes have been screened for their in microbiological activities against some kind of bacteria (G+ & G−) and fungi. For instance, in vitro anti-cancer activity of the gallium(III) complex was screened against the human hepato cellular carcinoma (HepG-2) tumor cell line.

Design, synthesis and pharmacological evaluation of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives as potential antitumor agents

A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a1−5d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that 5a3 exhibited effective inhibition on tumor growth in the NCI-H460 xenograft mouse model and that 5d3 displayed excellent antiproliferative activity in the BEL-7402 xenograft model. These results suggested that both 5a3 and 5d3 could be used as anticancer drug candidates. Mechanistic studies suggested that compounds 5a3 and 5d3 exerted their antitumor activity by up-regulation of Bax, intracellular Ca2+ release, ROS generation, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, inhibition of CDK activity and activation of the p53 protein.

Two pairs of phenylpropanoid enantiomers from the leaves of Eucommia ulmoides

Two pairs of phenylpropanoid enantiomers, (+)-(7S,8S)-alatusol D (1a), (−)-(7R,8R)-alatusol D (1b), (−)-(7S,8R)-alatusol D (2a) and (+)-(7R,8S)-alatusol D (2b) were isolated from the leaves of Eucommia ulmoides Oliver. Among them, 1a and 2b were firstly obtained by chiral enantiomeric resolution. Their structures were elucidated based on extensive spectroscopic analysis and the induced CD (ICD) spectrum caused by adding Mo2(AcO)4 in DMSO. All compounds were tested on Hep G2 tumor cell lines. However, none of the compounds showed potential cytotoxic activity against Hep G2 in vitro.

Biogenic Synthesis of Novel Functionalized Selenium Nanoparticles by Lactobacillus casei ATCC 393 and Its Protective Effects on Intestinal Barrier Dysfunction Caused by Enterotoxigenic Escherichia coli K88.

Selenium (Se) is an essential element for human and animal health. Biogenic selenium nanoparticles (SeNPs) by microorganism possess unique physical and chemical properties and biological activities compared with inorganic Se and organic Se. The study was conducted to investigate the mainly biological activities of SeNPs by Lactobacillus casei ATCC 393 (L. casei 393). The results showed that L. casei 393 transformed sodium selenite to red SeNPs with the size of 50–80 nm, and accumulated them intracellularly. L. casei 393-SeNPs promoted the growth and proliferation of porcine intestinal epithelial cells (IPEC-J2), human colonic epithelial cells (NCM460), and human acute monocytic leukemia cell (THP-1)-derived macrophagocyte. L. casei 393-SeNPs significantly inhibited the growth of human liver tumor cell line-HepG2, and alleviated diquat-induced IPEC-J2 oxidative damage. Moreover, in vivo and in vitro experimental results showed that administration with L. casei 393-SeNPs protected against Enterotoxigenic Escherichia coli K88 (ETEC K88)-caused intestinal barrier dysfunction. ETEC K88 infection-associated oxidative stress (glutathione peroxidase activity, total superoxide dismutase activity, total antioxidant capacity, and malondialdehyde) was ameliorated in L. casei 393-SeNPs-treated mice. These findings suggest that L. casei 393-SeNPs with no cytotoxicity play a key role in maintaining intestinal epithelial integrity and intestinal microflora balance in response to oxidative stress and infection.

Glucose-regulated protein of 94 kDa contributes to the development of an aggressive phenotype in breast cancer cells.

Grp94 plays an essential role in protein assembly. We previously suggested that Grp94 overexpression is involved in tumor aggressiveness. However, the underlying mechanisms remain unknown. Since many tumors display high Grp94 levels, we investigated the effects of tumor microenvironment on the regulation of this chaperone expression. First, we found out that hypoxia did not change Grp94 expression in the human tumor cell lines MCF-7 (breast cancer) and HepG2 (liver cancer). Second, glucose deprivation significantly increased Grp94 protein levels. Subsequently, we focused in the putative role of Grp94 in the acquisition of an aggressive phenotype by cancer cells. Using a more aggressive cancer cell model (MDA-MB-231 breast tumor cells), we found out that Grp94 knockdown using siRNA decreased the invasive capacity of cancer cells. Moreover, cells with decreased Grp94 levels displayed an enhanced sensitivity of tumor cells to doxorubicin, a standard drug in the treatment of breast cancer. Taken together, our results suggest that the expression of Grp94 is linked to tumor aggressiveness. Therefore, targeting Grp94 could be an effective way to inhibit tumor growth improving chemotherapy outcome.