Identification of miRNA signatures and their therapeutic potentials in prostate cancer

Molecular Biology Reports - Herein, we identified miRNA signatures that were able to differentiate malignant prostate cancer from benign prostate hyperplasia and revealed the therapeutic potential...     

Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells

Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect.     

The effect of pretreatment or combined treatment of quercetin on menadione toxicity in rat primary mixed glial cells in vitro

Neurons and glia are highly susceptible to reactive oxygen species that play a key role in various neurodegenerative diseases. Menadione, a synthetic derivative of vitamin K, induces reactive oxygen generation. Quercetin one of the most ubiquitous bioflavonoids in food of plant origin, has strong antioxidant activities on different cell types, however recent studies demonstrated that it has also prooxidant and cytotoxic potentials. We examined the action of pre- and co-treatment of quercetin on menadione induced glial toxicity. The primary mixed glial cells obtained from 1 to 3 day old rat brain were pretreated with 10, 25, 100 or 250 μM quercetin for 1 h, washed out and 10, 25, 50, 75 or 100 μM menadione was added for 6 h. The other group of cells was treated with respective doses of quercetin combined simultaneously with the same doses of menadione for 6 h. The cells were washed and incubated for additional 24 h for recovery period and the viability was measured by using MTT assay. Menadione was dose-dependently toxic to glia cells and pretreatment with respective quercetin doses for 1 h could not eliminate this toxicity. Although 10 and 25 μM quercetin combined with 10 and 25 μM menadione could not change, 100 and 250 μM quercetin together with 10 or 25 μM menadione for 6 h increased further the menadione induced toxicity. We conclude that when combined with menadione, quercetin at high doses could be toxic to primary rat glia cells in culture.     

The mitogenic activity of endothelin-1 on megakaryocytopoiesis in vitro

Endothelin (ET)-1 induces proliferation of various cells including smooth muscle cells, fibroblasts, glomerular mesangial cells, endothelial cells and osteoblasts. ET-1 also stimulates synthesis of interleukin (IL)-6 in endothelial and bone marrow stromal cells of rat. It is well known that IL-6 modulates megakaryocytopoiesis. Some studies have indicated that megakaryocytes express both ET receptors and they are targets for ET. Therefore we planned to examine the effects of ET-1 on the growth of normal megakaryocytic cells in rat bone marrow primary cell culture. Bone marrow cells were cultured at 37 degrees C, in an incubator atmosphere of 5% CO2 in air and 95% relative humidity for nine days. ET-1 at 10(-7), 10(-8 ) and 10(-11) M, and control with saline were added at the beginning of the experiment protocol. At each day, plasma clots were stained using direct-coloring thiocholin method for acetylcholinesterase activity. Although 10(-7) M ET-1 did not change the proliferation of megakaryocytic cells, this could be due to the presence of over crowded fibroblasts in the same environment. 10(-8) M ET-1 stimulated megakaryocytic cell growth to 234% over the control on the fifth day. ET-1 at a concentration of 10(-11) M also rised the megakaryocytic cell number significantly reaching up to 86% at the sixth day. Our results indicate that ET-1 may modulate the growth of megakaryocytic cells by an autocrine and/or paracrine action.     

Quercetin both partially attenuates hydrogen peroxide-induced toxicity and decreases viability of rat glial cells

Quercetin is one of the most ubiquitous flavonoids in foods of plant origin. Although quercetin is generally considered to provide protection against oxidative injury, recent studies have shown to be cytotoxic to many cell types. We intended here to determine whether quercetin protects against H2O2-induced toxicity and/or affects viability of rat mixed glial cells. The cells were obtained from 1-3 day olds rat brains and incubated in a humidified atmosphere of 5% CO2, at 37 °C in flasks. In the quercetin groups, different quercetin concentrations (1, 10, 50, 75 or 100 μM) were applied alone for 24 h. For H2O2 cytotoxicity group, the glial cells were treated for 3 h with 100 μM H2O2 which induced 75% cell death. In another group, the cells were treated with 100 μM H2O2 plus respective quercetin concentrations simultaneously for 3 h, the medium was removed and refed for 24 h. MTT test was then applied and statistical significance was ascertained by one way analysis of variance, followed by Tukey's multiple comparison test. Quercetin starting from 50 μM decreased the glia survival significantly. In H2O2 plus quercetin co-treated groups, both 75 and 100 μM quercetin attenuated toxic effect of H2O2 by 15%. In conclusion, quercetin both partially protects H2O2-induced gliotoxicity and decreases rat glial cell viability in primary culture.     

Protective Effect of Zinc on Cyclophosphamide-Induced Hematoxicity and Urotoxicity

Cyclophosphamide (CP) is widely used for the treatment of neoplastic diseases; however, its toxicity causes dose-limiting side effects. Zinc (Zn) is an essential trace element and has important biological functions that control many cell processes including DNA synthesis, normal growth, reproduction, fetal development, bone formation, and wound healing. Therefore, the toxicity of CP and the possible protective effect of Zn on blood cells, bone marrow, and bladder of rat were investigated in this study. Intraperitoneal administration of 50, 100, or 150 mg/kg CP for 3 days caused, in a dose-dependent manner, reductions in the number of leukocytes, thrombocytes, and bone marrow nucleated cells and a serious urotoxicity. To explore whether CP-induced damages could be prevented by Zn, other groups of rats were pretreated with 4 or 8 mg/kg ZnCl2 intraperitoneally for 3 days then challenged with respective doses of CP plus ZnCl2 on day 4 for three more days. The results indicated that treatment of rats with Zn could dose-dependently alleviate CP-induced toxicities on blood cells, bone marrow cells, and urinary bladder. We suggest that Zn could be a potentially effective drug in the prevention of CP-related hematoxicity and urotoxicity.     

Syntheses,characterization, antimicrobial and cytotoxic activities of pyridine-2,5-dicarboxylate complexes with 1,10-phenanthroline

In this study, four mononuclear M(II)-pyridine-2,5-dicarboxylate (M = Co(II), Ni(II), Cu(II) and Zn(II) complexes with pyridine-2,5-dicarboxylic acid or isocinchomeronic acid, 1,10-phenanthroline (phen), [Co(Hpydc)₂(phen)]·H₂O (1), [Ni(pydc)(phen)₂]·6.5H₂O (2) [Cu(pydc)(phen)(H₂O)₂] (3) and [Zn(pydc)(phen)(H₂O)₂]·H₂O (4) have been synthesized. Elemental, thermal and mass analyses, molar conductance, magnetic susceptibilities, IR and UV/vis spectroscopic studies have been performed to characterize the complexes. Subsequently, these ligands and complexes were tested for antimicrobial activity by disc diffusion method on Gram positive, negative bacteria and yeast. In addition, cytotoxic activity tests were performed on rat glioma (C6) cells by MTT viability assay for 24 and 48 h. Antimicrobial activity results demonstrated that when compared to the standard antibiotics, phen displayed the most effective antimicrobial effect. The effect of synthesized complexes was close to phen or less. Cytotoxic activity results showed that IC₅₀ value of phen was determined as 31 μM for 48 h. (1) and (2) compared to the alone ligand had less toxic activity. IC₅₀ values of (3) for 24 and 48 h treatments were 2.5 and 0.6 μM, respectively. IC₅₀ value of (4) for 48 h was 15 μM. In conclusion, phen, (3) and (4) may be useful as antibacterial and antiproliferative agents in the future.     

Protective effects of doxycycline in ischemia/reperfusion injury on kidney

Renal ischemia and reperfusion injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. The aim of this study was to evaluate whether doxycycline, a member of the tetracycline family of antibiotics, protects kidney tissue or not. 36 Sprague-Dawley rats (200–250 g) were used. The animals were divided into three groups: control, ischemia/reperfusion and ischemia/reperfusion+doxycycline group. Rats were subjected to renal ischemia by clamping the left pedicle for 1 h, and then reperfused for 1 h. The ischemia/reperfusion+doxycycline group were pretreated intraperitoneally with doxycycline suspension (10 mg/kg) 2 h before the induction of ischemia. Our results indicate that malondialdehyde, matrix-metalloproteinase-2, interleukin-2, interleukin-6, interleukin-10, interleukin 1-beta and tumor necrosis factor-alpha levels were significantly higher in the ischemia/reperfusion group than those in the control group. Doxycycline administration significantly decreased these parameters. Tissue inhibitor of metalloproteinases-1 levels also increased after ischemia/reperfusion and decreased with doxycycline pretreatment, but these changes were not significantly different. Glutathione levels significantly decreased after ischemia/reperfusion injury when compared with the control group and doxycycline pretreatment significantly increased glutathione levels when compared with the ischemia/reperfusion group. Apoptotic cells and p53 positive cells were significantly decreased in doxycycline treated group. These results suggest that doxycycline reduces renal oxidative injury and facilitates repair. Doxycycline may play a role in a renoprotective therapeutic regimen.     

The actions of leptin on survival and hydrogen peroxide toxicity in primary mixed glial cells of rat

Studies indicate that leptin is involved in not only energy expenditure and food intake, but also in protection against apoptosis, in inflammation and in stimulation of proliferation in many cell types. However, leptin treatment increases the oxidative stress in many cell culture studies. This contradiction evoked a question of whether leptin acts as an oxidant or antioxidant on glial cells. We investigated the effect of leptin on glial cell survival and hydrogen peroxide (H₂O₂)-induced toxicity in vitro. The survival rate of the cells was determined by using 3-(4,5-D-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thyazolyl blue (MTT) method. The cells obtained from the whole brain of 1–3 day-old rat were treated with 1, 10, 100 and 1000 ng/mL leptin for 24 or 72 h. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H₂O₂ or well known antioxidant glutathione (GSH) were applied to the cells. Malondialdehyde (MDA) levels were measured in cell lysates to which leptin was added for 24 h. The 100 and 1000 ng/mL leptin treatment for 72 h increased the glial viability by 19% and 36%, respectively. The dose of H₂O₂ that killed 75% of the cells was determined as 100 μM. GSH at different doses was applied as a positive control to the cells and the dose of 500 μM completely eliminated toxic effect of 100 μM H₂O₂. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H₂O₂ could not eliminate H₂O₂-caused toxicity. Furthermore, respective leptin doses did not change the glia MDA level. We suggest that leptin can increase glia survival dose dependently, but can not eliminate H₂O₂-induced oxidation in primary mixed glial cell culture.