Inhibition of lipogenesis and induction of apoptosis by valproic acid in prostate cancer cells via the C/EBPα/SREBP-1 pathway

Lipid metabolism reprogramming is now accepted as a new hallmark of cancer.Hence,target-ing the lipogenesis pathway may be a potential avenue for cancer treatme...     

Activity of the α-glucoside transporter Agt1 in Saccharomyces cerevisiae cells during dehydration-rehydration events

Microbial cells can enter a state of anhydrobiosis under desiccating conditions. One of the main determinants of viability during dehydration-rehydration cycles is structural integrity of the plasma membrane. Whereas much is known about phase transitions of the lipid bilayer, there is a paucity of information on changes in activity of plasma membrane proteins during dehydration-rehydration events. We selected the α-glucoside transporter Agt1 to gain insights into stress mechanisms/responses and ecophysiology during anhydrobiosis. As intracellular water content of S. cerevisiae strain 14 (a strain with moderate tolerance to dehydration-rehydration) was reduced to 1.5 g water/g dry weight, the activity of the Agt1 transporter decreased by 10–15 %. This indicates that functionality of this trans-membrane and relatively hydrophobic protein depends on water. Notably, however, levels of cell viability were retained. Prior incubation in the stress protectant xylitol increased stability of the plasma membrane but not Agt1. Studies were carried out using a comparator yeast which was highly resistant to dehydration-rehydration (S. cerevisiae strain 77). By contrast to S. cerevisiae strain 14, there was no significant reduction of Agt1 activity in S. cerevisiae strain 77 cells. These findings have implications for the ecophysiology of S. cerevisiae strains in natural and industrial systems.     

Pyrones from the bark of Garcinia conrauana: Conrauanalactone,a novel C20 derived α-pyrone

Conrauanalactone has been isolated from the bark of Garcinia conrauana Engl. (Guttiferae) and identified, on the basis of spectral and chemical evidence, as 4-hydroxy-6-pentadecyl- 2-pyrone. Minor constituents of the bark have been identified as 5,7-dihydroxychromone and eriodictyol.     

Protective effect of α-mangostin derivatives on hypoxia/reoxygenation-induced apoptosis in H9C2 cells and their mechanism

In this study, 17 α-mangostin Boc amino acid/organic acid ester derivatives 1–17 were synthesized and subjected to cytotoxicity and cell viability screening assays. A hypoxia/reoxygenation model of cardiomyocyte injury was selected and compound 5 was found to have a better protective effect against hypoxia/reoxygenation-induced myocardial injury by prophylactic administration screening. The levels of LDH and CK-MB in extracellular fluid were detected by ELISA; apoptosis was detected by Hoechst3358/PI double staining, Annexin V-FITC/PI double staining and mitochondrial membrane potential; the expression of key proteins in PI3K/Akt signaling pathway was detected by western blot. The result showed that compound 5 was non-toxic and has a significant cytoprotection effect at concentrations of 1 μM and 10 μM, and reduced the levels of LDH and CK-MB in the extracellular fluid. Hoechst 33,258/PI double staining results showed that compound 5 treatment significantly reduced bright blue cell nuclei and had anti-apoptotic effects; flow cytometry results showed that compound 5 improved hypoxia/reoxygenation-induced mitochondrial membrane potential and thus apoptosis. The western blot results showed that compound 5 upregulated the levels of p-PI3K and p-Akt, decreased the expression of cleaved caspase-3, cleaved caspase-9 and increased the Bcl-2/Bax ratio in a concentration-dependent manner. In addition, compound 5 reversed the effect of the LY294002 inhibitor. The present study suggests that compound 5 may serve as a potential PI3K activator and a safe and effective lead compound for the treatment of cardiovascular disease.     

The α-mangostin prevention on cisplatin-induced apoptotic death in LLC-PK1 cells is associated to an inhibition of ROS production and p53 induction

Cisplatin (CDDP) is a widely useful chemotherapeutic agent for the treatment of tumors including lung, ovary and testis. Acute renal injury, however, is the main side effect observed after CDDP treatment. This side effect is related to the apoptotic death in proximal tubular cells in the kidney and p53 protein has a central role in this process. On the other hand, α-mangostin (α-M), a xanthone derived from the pericarp of mangosteen, exerts a renoprotective effect against cisplatin-induced renal damage in rats. The aim of this study was to evaluate whether α-M protects proximal tubule renal epithelial cells (LLC-PK1) from CDDP-induced apoptotic death. Cells were co-incubated with 5 μM α-M and 100 μM CDDP for 24 h. It was found that α-M attenuated the following alterations: the apoptotic cell death, the increase in reactive oxygen species (ROS), the glutathione depletion and the increase in p53 expression induced by CDDP. In conclusion, the preventive effect of α-M on CDDP-induced apoptotic death is associated to the inhibition of p53 expression and ROS generation.     

Corrinoids from Methanosarcina barkeri: Structure of the α-ligand

5-Hydroxybenzimidazole is the only base detected in cobamide compounds from methanol-grown Methanosarcina barkeri. 5-Hydroxybenzimidazolylcobamide accounted for about 83 and 90% of the total corrinoids of whole cells and cell-free extracts, respectively. Probably, the rest of the corrinoids are base-less.     

Metafectene is superior to lipofectamine in the transfection of Gsα prostate cancer cells

Transfection efficiency of the novel reagent metafectene has not been compared with that of lipofectamine in the published English literature. We used these agents to transfect two prostate cancer cell lines, PC3 and G_sα, with a deoxyribonucleic acid (DNA) expression vector that generates double-stranded ribonucleic acid (RNA) for RNA interference (RNAi). Cotransfection of the green fluorescent protein (GFP) reporter gene revealed that the mean (± standard deviation) transfection efficiencies with lipofectamine were 5.8±0.4% for PC3 cells and 3.6±1.5% for G_sα cells. Mean transfection efficiency with metafectene declined to 0.1±0% for PC3 cells but improved to 54.6±5.5% for G_sα cells. With G_sα cells, metafectene transfection of GFP plasmid alone yielded 46.9% positive cells, and cotransfection with CD44v9 expression vector yielded 45.9% positive cells. The visual impact of the transfected RNAi construct was detectable at the protein level 4 to 6 d posttransfection and was more dramatic after using metafectene than after using lipofectamine. Thus, in vitro, metafectene transfection efficiency was sufficient to allow us to assess the functional significance of our RNAi construct, suggesting metafectene as an excellent candidate for RNAi-mediated anticancer gene therapy.     

Study of the inclusion of the (R)- and (S)-camphor enantiomers in α-cyclodextrin by X-ray crystallography and molecular dynamics

The inclusion of (R)- and (S)-camphor compounds in α-cyclodextrin has been studied by X-ray crystallography. The crystal structures of the complexes reveal that one guest molecule is accommodated inside the cavity formed by a head-to-head cyclodextrin dimer. In the crystal lattice, the dimers form layers which are successively shifted by half a dimer. In both (R)- and (S)-cases, the camphor molecule exhibits disorder and occupies three major sites with orientations that can be described as either ‘polar’ or ‘equatorial’. Molecular dynamics simulations performed for the observed complexes indicate that although the carbonyl oxygen of both (R)- and (S)-camphor switches between different hydrogen bonding partners, it maintains the observed mode of ‘polar’ or ‘equatorial’ alignment.     

The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells

Molecular and Cellular Biochemistry - The era of induced pluripotent stem cells (iPSCs) was used as novel biotechnology to replace embryonic stem cells bypassing the ethical concerns and problems...     

Inhibition of the α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat cells

Protein N-glycosylation plays very important roles in immunity and α-mannosidase is one of the key enzymes in Nglycosylation. This paper reports that inhibition of α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat T cells. In comparison to the controls with normal expression of the enzyme, Jurkat cells with the inhibition of Man2c1 gene expression （AS cell） formed larger aggregates in culture, indicating an enhancement of adhesion between the cells. mRNA differential display analysis discovered up-regulation of several adhesion molecule genes in the AS cell. Because of the pivotal role played by CD54-LFA-1 interaction in immune cell interaction, this study focused on the contribution of enhanced expression of CD54 and LFA-1 to the enhanced adhesion of AS Jurkat cells. These facts, including increased binding of AS cells to ICAM-1-Fc, Mg^2＋ activation of the binding of AS cells to ICAM-1-Fc and enhanced aggregation of AS cells, together with the inhibiting effect of a blocking CD1 la mAb on the binding to ICAM-1-Fc and aggregation of the cells demonstrate an important contribution of enhanced CD54-LFA-1 interaction to increased adhesion between AS cells. The enhanced CD54-LFA-1 interaction also resulted in increased adhesion between AS Jurkat T cells and Raji B cells. In addition, AS cells showed cytoskeletal rearrangement. The data imply a biological significance of MAN2C1 in T-cell functioning.     

Potentiation of paclitaxel effect by resveratrol in human breast cancer cells by counteracting the 17β-estradiol/estrogen receptor α/neuroglobin pathway

Neuroglobin (NGB), an antiapoptotic protein upregulated by 17β-estradiol (E2), is part of E2/estrogen receptor α (ERα) pathway pointed to preserve cancer cell survival in presence of microenvironmental stressors including chemotherapeutic drugs. Here, the possibility that resveratrol (Res), an anticancer plant polyphenol, could increase the susceptibility of breast cancer cells to paclitaxel (Pacl) by affecting E2/ERα/NGB pathway has been evaluated. In MCF-7 and T47D (ERα-positive), but not in MDA-MB 231 (ERα-negative) nor in SK-N-BE (ERα and ERβ positive), Res decreases NGB levels interfering with E2/ERα-induced NGB upregulation and with E2-induced ERα and protein kinase B phosphorylation. Although Res treatment does not reduce cell viability by itself, this compound potentiates Pacl proapoptotic effects. Notably, the increase of NGB levels by NGB expression vector transfection prevents Pacl or Res/Pacl effects. Taken together, these findings indicate a new Res-based mechanism that acts on tumor cells impairing the E2/ERα/NGB signaling pathways and increasing cancer cell susceptibility to chemotherapeutic agent.     

Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells

Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1α (HIF-1α) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1α protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1α protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1α protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2α (eIF-2α) which can cause inhibition of general protein synthesis. These results suggest that silibinin’s activity to inhibit HIF-1α protein expression is associated with the suppression of global protein translation.     

Inhibition of protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase by xanthones from Cratoxylum cochinchinense, and their kinetic characterization

Cratoxylum cochinchinense displayed significant inhibition against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase, both of which are key target enzymes to attenuate diabetes and obesity. The compounds responsible for both enzymes inhibition were identified as twelve xanthones (1–12) among which compounds 1 and 2 were found to be new ones. All of them simultaneously inhibited PTP1B with IC₅₀s of (2.4–52.5?µM), and α-glucosidase with IC₅₀ values of (1.7–72.7?µM), respectively. Cratoxanthone A (3) and γ-mangostin (7) were estimated to be most active inhibitors against both PTP1B (IC₅₀?=?2.4?µM for 3, 2.8?µM for 7) and α-glucosidase (IC₅₀?=?4.8?µM for 3, 1.7?µM for 7). In kinetic studies, all isolated xanthones emerged to be mixed inhibitors of α-glucosidase, whereas they behaved as competitive inhibitors of PTP1B. In time dependent experiments, compound 3 showed isomerization inhibitory behavior with following kinetic parameters: K_i^app?=?2.4?µM; k₅?=?0.05001?µM^?1?S^?1 and k₆?=?0.02076?µM^?1?S^?1.     

Novel α(2)β(1) integrin-targeted peptide probes for prostate cancer imaging

Accumulating experimental evidence indicates that overexpression of α(2)β(1) integrin may correlate with progression in human prostate cancer. The objective of this study was to design a novel imaging probe based on the Asp-Gly-Glu-Ala (DGEA) peptide for near-infrared-fluorescent (NIRF) imaging of α(2)β(1) integrin expression in prostate cancer. The peptides were conjugated with appropriate fluorescent dyes, and the binding affinity of these probes was evaluated by flow cytometry in three human prostate cell lines (PC-3, CWR-22, and LNCaP). In vivo NIRF imaging of the α(2)β(1)-positive PC-3 xenograft model was performed to evaluate the α(2)β(1) targeted probe. In vitro immunofluorescence staining was carried out to confirm the α(2)β(1) integrin expression level. Flow cytometry analysis showed that PC-3 had the highest probe uptake, followed by CWR-22 and LNCaP tumor cells. In the subcutaneous PC-3 model, the tumor demonstrated prominent uptake with good tumor to background contrast. Immunohistochemistry staining also supported the in vivo optical imaging results. DGEA-based optical agents have been developed for specific imaging of α(2)β(1) integrin expression. In vitro and in vivo localization demonstrated the potential of this agent to identify tumor subtypes amenable to anti-α(2)β(1) integrin treatment and potentially provide prognostic information regarding tumor progression.     

Do female fruit flies (Drosophila serrata) copy the mate choice of others?

Female mate-choice copying is a social learning phenomenon whereby a female's observation of a successful sexual interaction between a male and another female increases her likelihood of subsequently preferring that male. Although mate-choice copying has been documented in several vertebrate species, to our knowledge it has not yet been investigated in insects. Here, we investigated whether female mate-choice copying occurs in the fruit fly Drosophila serrata, a model system for the study of mate preferences and the sexual selection they generate. We used two complementary experiments in which focal females were given a choice between two males that differed in either their apparent (as determined visually by the focal female) or actual recent mating success. Mate-choice copying was evaluated by testing whether focal females mated more frequently with the ‘preferred’ male as opposed to the other male. In both experiments, however, we found no evidence for mate-choice copying. We discuss possible reasons for the apparent absence of mate-choice copying in this species.