Evaluating the Effects of Separate and Concomitant Use of MK-2206 and Salinomycin on Prostate Cancer Cell Line

Background:Prostate cancer is known as one of the most prevalent health disorders in the male population globally. The aim of the current study was to evaluate the effects of separate and concomitant use of MK-2206 and salinomycin on prostate cancer cell line.Methods:The antitumor potential of separate and concomitant use of MK-2206 and salinomycin was evaluated in a panel of prostate cancer cell line (PC-3). To get insights into the underlying mechanism of action, different assays including the rate of apoptosis, cell viability, and gene expression were performed in treated prostate cancer cells.Results:A significant reduction was detected in the viability percentage of prostate cancer cells (p< 0.001) and the rate of Akt expression (p< 0.001) in all salinomycin, MK-2206, and salinomycin+MK-2206 groups compared to the negative control group. Furthermore, in comparison with the negative control group, there was a notable increase in both the rate of Bad expression (p< 0.001) and prostate cancer cells apoptosis after salinomycin, MK-2206, and salinomycin+MK-2206 treatments. Moreover, the concomitant use of salinomycin+MK-2206 revealed synergistic improvements regarding the viability of prostate cancer cells and the rate of the Akt and Bad expressions compared to the separate administration of salinomycin and MK-2206 (all p< 0.05)Conclusion:The findings of the present study may contribute to improving the efficacy of the therapies regarding the management of prostate cancer and providing a beneficial strategy in clinical trials.Key Words: Apoptosis, Gene Expression, MK 2206, Prostatic Neoplasms, Salinomycin     

microRNAs: Key players in virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.     

MicroRNA-21 (miR-21) Regulates Cellular Proliferation,Invasion, Migration,and Apoptosis by Targeting PTEN,RECK and Bcl-2 in Lung Squamous Carcinoma,Gejiu City,China

Background

In South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). Research has demonstrated that overexpression of miR-21 occurs in many cancers. However, the unique relationship between miR-21 and its target genes in GSQCLC has never been investigated. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets.

Methodology/Principal Findings

In the current study, we initially found overexpression of miR-21 occurring in non-small cell lung cancer (NSCLC) cell lines when compared to the immortalized lung epithelial cell line BEAS-2B. We also demonstrated that high expression of miR-21 could increase tumor cell proliferation, invasion, viability, and migration in GSQCLC cell line (YTMLC-90) and NSCLC cell line (NCI-H157). Additionally, our results revealed that miR-21 could suppress YTMLC-90 and NCI-H157 cell apoptosis through arresting cell-cycle at G₂/M phase. Furthermore, we demonstrated that PTEN, RECK and Bcl-2 are common target genes of miR-21 in NSCLC. Finally, our studies showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and decrease in Bcl-2 at the mRNA and protein level in YTMLC-90 and NCI-H157 cell lines. However, we have not observed any remarkable difference in the levels of miR-21 and its targets in YTMLC-90 cells when compared with NCI-H157 cells.

Conclusions/Significance

miR-21 simultaneously regulates multiple programs that enhance cell proliferation, apoptosis and tumor invasiveness by targeting PTEN, RECK and Bcl-2 in GSQCLC. Our results demonstrated that miR-21 may play a vital role in tumorigenesis and progression of lung squamous cell carcinoma and suppression of miR-21 may be a novel approach for the treatment of lung squamous cell carcinoma.     

Biological roles of titanium

Ti⁴⁺ in soil is a natural antibiotic mobilized by bacteria-generated H⁺. When added to the diet of young mice, Ti⁴⁺ enhanced their growth. These and observations of others indicate that Ti⁴⁺ has a variety of biological roles.     

Peptides with Dual Antimicrobial-Anticancer Activity Derived from the N-terminal Region of H. pylori Ribosomal Protein L1 (RpL1)

International Journal of Peptide Research and Therapeutics - Whereas the traditional approaches of cancer therapy including radiotherapy, chemotherapy, and immunotherapy have failed to properly...     

A kinetic spectrophotometric method for simultaneous determination of glycine and lysine by artificial neural networks

A spectrophotometric method for simultaneous analysis of glycine and lysine is proposed by application of neural networks on the spectral kinetic data. The method is based on the reaction of glycine and lysine with 1,2-naphthoquinone-4-sulfonate (NQS) in slightly basic medium. On the basis of the difference in the rate between the two reactions, these two amino acids can be determined simultaneously in binary mixtures. Feed-forward neural networks have been trained to quantify considered amino acids in mixtures under optimum conditions. In this way, a one-layer network was trained. Sigmoidal and linear transfer functions were used in the hidden and output layers, respectively. Linear calibration graphs were obtained in the concentration range of 1 to 25microgml(-1) for glycine and 1 to 19microgml(-1) for lysine. The analytical performance of this method was characterized by the relative standard error. The proposed method was applied to the determination of considered amino acids in synthetic samples.     

PET imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk reporter gene expression in mice and humans using [18F]FHBG

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) positron emission tomography (PET) reporter gene (PRG) or its mutant HSV1-sr39tk are used to investigate intracellular molecular events in cultured cells and to image intracellular molecular events and cell trafficking in living subjects. The expression of these PRGs can be imaged using 18F- or 124I-radiolabeled acycloguanosine or pyrimidine analog PET reporter probes (PRPs). This protocol describes the procedures for imaging HSV1-tk or HSV1-sr39tk PRG expression in living subjects with the acycloguanosine analog 9-4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG). [18F]FHBG is a high-affinity substrate for the HSV1-sr39TK enzyme with relatively low affinity for mammalian TK enzymes, resulting in improved detection sensitivity. Furthermore, [18F]FHBG is approved by the US Food and Drug Administration as an investigational new imaging agent and has been shown to detect HSV1-tk transgene expression in the liver tumors of patients. MicroPET imaging of each small animal can be completed in approximately 1.5 h, and each patient imaging session takes approximately 3 h.     

Structural studies of hen egg-white lysozyme dimer: comparison with monomer

A facile method for the formation of covalent bonds between protein molecules is zero length cross-linking. This method enables the formation of cross-links without use of any chemical reagents. Here, we report a cross-linking method for lysozyme and some structural studies as well as catalytic activity assay was performed on lysozyme dimer. The results showed that catalytic activity of lysozyme dimer was the same as monomer. Also, the GdnCl-induced equilibrium unfolding of hen egg-white lysozyme monomer and dimer at pH 2 was studied over a temperature range of 290.7-303.2 K by means of CD spectroscopy. The lack of coincidence between two unfolding curves at 222 and 289 nm in lysozyme dimer was observed, which suggested the existence of intermediate state in unfolding process, while lysozyme monomer showed a single cooperative transition. Thus, the thermodynamic parameters were estimated on the basis of two-state mechanism for lysozyme monomer and three-state one for lysozyme dimer. These results indicated that zero length cross-linking can stabilize the intermediate, so the population of intermediate increased. Our results offer a special opportunity to study the role of intermediates in protein folding mechanisms. In addition thermal unfolding of monomer and dimer in 222 nm was achieved.     

Potassium solubilising bacteria (KSB) isolated from rice paddy soil: from isolation,identification to K use efficiency

The present study was intended to isolate potassium-solubilizing bacteria (KSB) from paddy rhizosphere soil. The isolates were obtained from 40 rice paddy fields across Mazandaran province in northern Iran and screened for their K-solubilizing ability on modified Aleksandrov agar medium. The three selected isolates which showed the best solubilisation of potassium were identified using molecular marker 16S rDNA sequencing. The isolates were identified as Pantoea agglomerans, Rahnella aquatilis and Pseudomonas orientalis. From the flame photometry results, the amounts of potassium released by the isolates from mica at 21st day of incubation were 35.36, 76.04 and 56.58 μg ml^?1, respectively. The estimated optimal growth temperature (Ts) were 26.38, 29.17 and 26.80 °C based on segmented model analysis. The pH values of the culture medium with ranges from 6.75–7.26, had a more positive effect on the solubilization of potassium-bearing minerals. The pot experiment results showed that the inoculums of all three KSB enhanced the amount of grain yield and K uptake compared to the control treatment (without K fertilizer). Values were higher when KSB inoculums were used with ½ K chemical fertilizer (47.5 Kg/ha). Bacterial inoculums also increased K use efficiency (AE, PE, APE, ARE and UE) in plants. In conclusion, these findings have successfully demonstrated the effectiveness of locally isolated PGPR with multiple beneficial characteristics such as K solubilizing, IAA production and tolerance to different environment stresses. Therefore, they can be used as biofertilizers to enhance the availability of potassium in the soils and to improve the growth and yield of rice.     

Investigation into the Anticancer Activity and Apoptosis Induction of Brevinin-2R and Brevinin-2R-Conjugated PLA–PEG–PLA Nanoparticles and Strong Cell Cycle Arrest in AGS,HepG2 and KYSE-30 Cell Lines

International Journal of Peptide Research and Therapeutics - Our study aims to establish a biocompatible nanostructure for the improved delivery of anticancer peptide, Brevinin-2R, to treat human...