On the mechanism of miR-29b enhancement of etoposide toxicity in vitro.

MicroRNA hsa-miR-29 was connected to a number of malignancies. Its target genes are many, among them Mcl-1 that is expressed in three possible isoforms, one of which is anti-apoptotic and another one pro-apoptotic. Ratio of these two isoforms appears to affect cell response to external stimuli.

Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular Ca elevations and mitochondrial depolarisation.

Background And Aim: Osmotic changes represent a burden for the body and their limitation would be beneficial. We hypothesized that ubiquitous natural compounds could guard against cytotoxic effects of osmotic stress. We evaluated the anti-hypertonic mechanism of quercetin and 2,3-dehydrosilybin in H9c2 cells in vitro.

Hepatic biotransformation of non-psychotropic phytocannabinoids and activity screening on cytochromes P450 and UDP-glucuronosyltransferases.

This study examined the biotransformation of phytocannabinoids in human hepatocytes. The susceptibility of the tested compounds to transformations in hepatocytes exhibited the following hierarchy: cannabinol (CBN) > cannabigerol (CBG) > cannabichromene (CBC) > cannabidiol (CBD). Biotransformation included hydroxylation, oxidation to a carboxylic acid, dehydrogenation, hydrogenation, dehydration, loss/shortening of alkyl, glucuronidation and sulfation.

Dual Effect of Taxifolin on ZEB2 Cancer Signaling in HepG2 Cells.

Polyphenols, secondary metabolites of plants, exhibit different anti-cancer and cytoprotective properties such as anti-radical, anti-angiogenic, anti-inflammation, or cardioprotective. Some of these activities could be linked to modulation of miRNAs expression. MiRNAs play an important role in posttranscriptional regulation of their target genes that could be important within cell signalling or preservation of cell homeostasis, e.

Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro.

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS).

The effect of quercetin on microRNA expression: A critical review.

Quercetin, a flavonoid with multiple proven health benefits to both man and animals, displays a plethora of biological activities, collectively referred to as pleiotropic. The most studied of these are antioxidant and anti-inflammatory but modulation of signalling pathways is important as well. One of the lesser-known and recently discovered roles of quercetin, is modulation of microRNA (miRNA) expression.

Cardioprotective effect of 2,3-dehydrosilybin preconditioning in isolated rat heart.

2,3-dehydrosilybin (DHS) is a minor component of silymarin, Silybum marianum seed extract, used in some dietary supplements. One of the most promising activities of this compound is its anticancer and cardioprotective activity that results, at least partially, from its cytoprotective, antioxidant, and chemopreventive properties. The present study investigated the cardioprotective effects of DHS in myocardial ischemia and reperfusion injury in rats.

Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug transport.

Etoposide is a well-known and widely used anticancer drug that displays several side effects. In addition, tumors often acquire resistance to this drug. Our aim is to develop a combination therapy that would augment toxicity of etoposide in malignant cells.

On the causes and consequences of the uncoupler-like effects of quercetin and dehydrosilybin in H9c2 cells.

Quercetin and dehydrosilybin are polyphenols which are known to behave like uncouplers of respiration in isolated mitochondria. Here we investigated whether the effect is conserved in whole cells. Following short term incubation, neither compound uncouples mitochondrial respiration in whole H9c2 cells below 50μM.

MicroRNA hsa-miR-29b potentiates etoposide toxicity in HeLa cells via down-regulation of Mcl-1.

Etoposide is commonly used as a monotherapy or in combination with other drugs for cancer treatments. In order to increase the drug efficacy, ceaseless search for novel combinations of drugs and supporting molecules is under way. MiRNAs are natural candidates for facilitating drug effect in various cell types.

Polyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity.

A recent study showed that silymarin, a standardized extract of S. marianum might be used in the prevention of equine laminitis. We investigated the effects of quercetin and some compounds found in silymarin (silybin, taxifolin and dehydrosilybin) on reactive oxygen species (ROS) production and myeloperoxidase (MPO) release by stimulated equine neutrophils (PMNs) and on MPO activity.

Silymarin Constituent 2,3-Dehydrosilybin Triggers Reserpine-Sensitive Positive Inotropic Effect in Perfused Rat Heart.

2,3-dehydrosilybin (DHS) is a minor flavonolignan component of Silybum marianum seed extract known for its hepatoprotective activity. Recently we identified DHS as a potentially cardioprotective substance during hypoxia/reoxygenation in isolated neonatal rat cardiomyocytes. This is the first report of positive inotropic effect of DHS on perfused adult rat heart.

Silymarin component 2,3-dehydrosilybin attenuates cardiomyocyte damage following hypoxia/reoxygenation by limiting oxidative stress.

Ischemic postconditioning and remote conditioning are potentially useful tools for protecting ischemic myocardium. This study tested the hypothesis that 2,3-dehydrosilybin (DHS), a flavonolignan component of Silybum marianum, could attenuate cardiomyocyte damage following hypoxia/reoxygenation by decreasing the generation of reactive oxygen species (ROS). After 5-6 days of cell culture in normoxic conditions the rat neonatal cardiomyocytes were divided into four groups.

The role of miR-29 family members in malignant hematopoiesis.

Aims: MicroRNAs of the miR-29 family members were one of the first microRNAs identified as possible therapeutic agents in malignant hematopoiesis. The aim of our review is to summarize the current state of knowledge on miR-29 family members.

Methods: We performed literature searches involving miR-29 family members and their relationship to individual hematological malignancies, namely acute myeloid leukemia (AML), chronic lymphoblastic leukemia (CLL) and chronic myeloid leukemia (CML).

Silymarin and its constituents in cardiac preconditioning.

Silymarin, a standardised extract of Silybum marianum (milk thistle), comprises mainly of silybin, with dehydrosilybin (DHSB), quercetin, taxifolin, silychristin and a number of other compounds which are known to possess a range of salutary effects. Indeed, there is evidence for their role in reducing tumour growth, preventing liver toxicity, and protecting a number of organs against ischemic damage. The hepatoprotective effects of silymarin, especially in preventing Amanita and alcohol intoxication induced damage to the liver, are a well established fact.

Biotransformation of silybin and its congeners.

Silybin and its congeners belong to a group of flavonolignans with strong biological activities. These compounds are potentially applicable in human medicine, e. g.

Expression of miR-15a and miR-16-1 in patients with chronic lymphocytic leukemia.

Introduction: MicroRNAs (miRNAs) are small non-coding single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. In the pathogenesis of chronic lymphocytic leukemia (CLL), miR-15a and miR-16-1 play an important role. These miRNAs are located on chromosome 13 in the 13q14.

Protopine and allocryptopine increase mRNA levels of cytochromes P450 1A in human hepatocytes and HepG2 cells independently of AhR.

The isoquinoline alkaloids protopine and allocryptopine are present in phytopreparations from medicinal plants, such as Fumaria officinalis. Since nothing is known about effects of the alkaloids on the expression of xenobiotic-metabolizing enzymes, we examined whether protopine or allocryptopine affect the expression of cytochromes P450 (CYPs) 1A1 and 1A2 in primary cultures of human hepatocytes and human hepatoma HepG2 cells. In HepG2 cells, protopine and allocryptopine significantly increased CYP1A1 mRNA levels after 24h exposure at concentrations from 25 and 10 μM, respectively, as shown by real-time PCR.

Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism.

Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence.

Ion-trap mass spectrometry for determination of 3,5,3'-triiodo-L-thyronine and 3,5,3',5'-tetraiodo-L-thyronine in neonatal rat cardiomyocytes.

Our short report describes a method employing electrospray ion-trap mass spectrometry (MS) connected to a reversed phase (C(8)) HPLC system for monitoring of 3,5,3'-triiodo-L-thyronine (T3) and its precursor 3,5,3',5'-tetraiodo-L-thyronine (T4) in neonatal rat cardiomyocytes. The experimental protocol allows simultaneous analysis of the free thyroid hormones in nanomolar concentration range and enables observation of their distribution in cultivation medium over time. The method is a useful tool for MS(2) identification of T3/T4 and analysis of their uptake into mammalian cells.

Uncouple my heart: the benefits of inefficiency.

Myocardial ischemia/reperfusion (IR) injury leads to structural changes in the heart muscle later followed by functional decline due to progressive fibrous replacement. Hence approaches to minimize IR injury are devised, including ischemic pre-and postconditioning. Mild uncoupling of oxidative phosphorylation is one of the mechanisms suggested to be cardioprotective as chemical uncoupling mimics ischemic preconditioning.

Modulation of UCP2 expression by p38--a link to cardioprotection.

Background: Discovery of uncoupling protein 2 (UCP2) in 1997 and demonstration of its wide tissue expression has triggered an important question about controlled oxidative phosphorylation uncoupling and the physiological function of this process. Uncoupling protein 2 (UcP2) is a mitochondrial protein that can influence the mitochondrial membrane potential and hence the production of reactive oxygen species by mitochondria. It is also thought to be involved in apoptotic signaling pathways and it has been suggested to be important in cardio- and neuroprotection.

Redistribution of cell death-inducing DNA fragmentation factor-like effector-a (CIDEa) from mitochondria to nucleus is associated with apoptosis in HeLa cells.

Cell death-inducing DFF[DNA fragmentation factor]-like effector-a (CIDEa), may initiate apoptosis by disrupting a complex consisting of 40-kDa caspase-3-activated nuclease (DFF40/CAD) and its 45-kDa inhibitor (DFF45/ICAD). CIDEa, however, was found to be localized in mitochondria. We have performed immunodetection of CIDEa in whole cells and subcellular fractions of HeLa cells adapted for a tetracycline-inducible CIDEa expression.

Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells.

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells.