Roots Essential Oil: Chemical Composition, Antioxidant Activities, and Molecular Docking Studies on Enzymes Involved in Redox Biological Processes.

is usually employed in Peruvian folk medicine in the form of infusion to treat stomach pain, and has antispasmodic, relaxing, sleep-promoting, and sedative properties, as well as is an anti-inflammatory. In this study, essential oil (VPEO) was obtained by hydrodistillation, analyzed by GC and GC/MS, and 47 compounds were identified. Major oil components were α-patchoulene (5.

Antifungal Activity and In Silico Studies on 2-Acylated Benzo- and Naphthohydroquinones.

The high rates of morbidity and mortality due to fungal infections are associated with a limited antifungal arsenal and the high toxicity of drugs. Therefore, the identification of novel drug targets is challenging due to the several resemblances between fungal and human cells. Here, we report the in vitro antifungal evaluation of two acylphenols series, namely 2-acyl-1,4-benzo- and 2-acyl-1,4-naphthohydroquinones.

Inhibition of Growth by Redox Cycling Phenylaminojuglones.

Infection by increases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4-naphthoquinone, prevents growth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, and evaluation of a series of juglone derivatives, namely, 2/3-phenylaminojuglones, as potential growth inhibitors.

Evaluation of Potential Mechanisms Controlling the Catalase Expression in Breast Cancer Cells.

Development of cancer cell resistance against prooxidant drugs limits its potential clinical use. MCF-7 breast cancer cells chronically exposed to ascorbate/menadione became resistant (Resox cells) by increasing mainly catalase activity. Since catalase appears as an anticancer target, the elucidation of mechanisms regulating its expression is an important issue.

Catalase down-regulation in cancer cells exposed to arsenic trioxide is involved in their increased sensitivity to a pro-oxidant treatment.

Background: Pro-oxidant drugs have been proposed for treating certain cancers but the resistance developed by cancer cells to oxidative stress limits its potential use in clinics. To understand the mechanisms underlying resistance to oxidative stress, we found that the chronic exposure to an HO-generating system (ascorbate/menadione, Asc/Men) or catalase overexpression (CAT3 cells) increased the resistance of cancer cells to oxidative stress, likely by increasing the antioxidant status of cancer cells.

Methods: Modulation of catalase expression was performed by either protein overexpression or protein down-regulation using siRNA against catalase and aminotriazole as pharmacological inhibitor.

Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach.

This review is centered on the antioxidant enzyme catalase and will present different aspects of this particular protein. Among them: historical discovery, biological functions, types of catalases and recent data with regard to molecular mechanisms regulating its expression. The main goal is to understand the biological consequences of chronic exposure of cells to hydrogen peroxide leading to cellular adaptation.

Silibinin induces hepatic stellate cell cycle arrest via enhancing p53/p27 and inhibiting Akt downstream signaling protein expression.

Background: Proliferation of hepatic stellate cells (HSCs) plays a pivotal role in the progression of liver fibrosis consequent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs.

Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to HO (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription.

In vivo inhibition of tumor progression by 5 hydroxy-1,4-naphthoquinone (juglone) and 2-(4-hydroxyanilino)-1,4-naphthoquinone (Q7) in combination with ascorbate.

The purpose of the study was to obtain further in vivo data of antitumor effects and mechanisms triggered by juglone and Q7 in combination with ascorbate. The study was done using Ehrlich ascites tumor-bearing mice. Treatments were intraperitoneal every 24 h for 9 days.

High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver.

Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1MPa) for each ten-meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked.

Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) and genomic gain of the NQO1 locus modulates breast cancer cell sensitivity to quinones.

Aims: Alterations in the expression of antioxidant enzymes are associated with changes in cancer cell sensitivity to chemotherapeutic drugs (menadione and β-lapachone). Mechanisms of acquisition of resistance to pro-oxidant drugs were investigated using a model of oxidative stress-resistant MCF-7 breast cancer cells (Resox cells).

Main Methods: FISH experiments were performed in tumor biopsy and breast cancer cells to characterize the pattern of the NQO1 gene.

Binding of dihydroxynaphthyl aryl ketones to tubulin colchicine site inhibits microtubule assembly.

Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed among the assayed compounds seem to be related to the structure and position of the aryl substituent bonded to the carbonyl group.

Regulation of catalase expression in healthy and cancerous cells.

Catalase is an important antioxidant enzyme that dismutates hydrogen peroxide into water and molecular oxygen. The catalase gene has all the characteristics of a housekeeping gene (no TATA box, no initiator element sequence, high GC content in promoter) and a core promoter that is highly conserved among species. We demonstrate in this review that within this core promoter, the presence of DNA binding sites for transcription factors, such as NF-Y and Sp1, plays an essential role in the positive regulation of catalase expression.

DNA damage and inhibition of akt pathway in mcf-7 cells and ehrlich tumor in mice treated with 1,4-naphthoquinones in combination with ascorbate.

The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation.

AICAR induces Nrf2 activation by an AMPK-independent mechanism in hepatocarcinoma cells.

Hepatocellular carcinoma is one of the most frequent tumor types worldwide and oxidative stress represents a major risk factor in pathogenesis of liver diseases leading to HCC. Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor activated by oxidative stress that governs the expression of many genes which constitute the antioxidant defenses of the cell. In addition, oxidative stress activates AMP-activated protein kinase (AMPK), which has emerged in recent years as a kinase that controls the redox-state of the cell.

Substituted 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death.

Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3‑acyl‑2‑phenylamino‑1,4‑naphthoquinones (DPB1‑DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor‑bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM).

Catalase expression in MCF-7 breast cancer cells is mainly controlled by PI3K/Akt/mTor signaling pathway.

Catalase is an antioxidant enzyme that catalyzes mainly the transformation of hydrogen peroxide into water and oxygen. Although catalase is frequently down-regulated in tumors the underlying mechanism remains unclear. Few transcription factors have been reported to directly bind the human catalase promoter.

Eco-friendly synthesis and antiproliferative evaluation of some oxygen substituted diaryl ketones.

A broad variety of oxygen-substituted diaryl ketones has been synthesized by solar energy-induced Friedel Crafts acylations of 1,4-benzo- and 1,4-naphthoquinones with benzaldehydes. The in vitro antiproliferative properties of the photoproducts were assessed on prostate (DU-145), bladder (T24) and breast (MCF7) human-derived tumor cell lines and compared to non-tumor mouse fibroblasts (Balb/3T3). Among the tested compounds, it was found that those containing a 3,4,5-trimethoxyphenyl A-ring, such as 12 and 22 are more active on DU-145, with EC50 values of 1.

Role of AMPK activation in oxidative cell damage: Implications for alcohol-induced liver disease.

Chronic alcohol consumption is a well-known risk factor for liver disease. Progression of alcohol-induced liver disease (ALD) is a multifactorial process that involves a number of genetic, nutritional and environmental factors. Experimental and clinical studies increasingly show that oxidative damage induced by ethanol contributes in many ways to the pathogenesis of alcohol hepatoxicity.

Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis.

Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na(3)VO(4)) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na(3)VO(4) was cytotoxic against T24 cells (EC(50)=5.

Precision-cut liver slices to investigate responsiveness of deep-sea fish to contaminants at high pressure.

While deep-sea fish accumulate high levels of persistent organic pollutants (POPs), the toxicity associated with this contamination remains unknown. Indeed, the recurrent collection of moribund individuals precludes experimental studies to investigate POP effects in this fauna. We show that precision-cut liver slices (PCLS), an in vitro tool commonly used in human and rodent toxicology, can overcome such limitation.

Hsp90 is cleaved by reactive oxygen species at a highly conserved N-terminal amino acid motif.

Hsp90 is an essential chaperone that is necessary for the folding, stability and activity of numerous proteins. In this study, we demonstrate that free radicals formed during oxidative stress conditions can cleave Hsp90. This cleavage occurs through a Fenton reaction which requires the presence of redox-active iron.

Evaluation of analgesic activities of tremetone derivatives isolated from the Chilean altiplano medicine Parastrephia lepidophylla.

Parastrephia lepidophylla, family Asteraceae, has ancient use in traditional medicine in the region of Tarapacá, Chile. Bioguided fractionation of extracts of this plant was undertaken in the search for compounds with analgesic and antioxidant activity. Two benzofuran derivatives were isolated as the major components of this plant, identified as tremetone 1 and methoxytremetone 6.

Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp.

Tumor reoxygenation following administration of Mitogen-Activated Protein Kinase inhibitors: a rationale for combination with radiation therapy.

Background And Purpose: The relevance of Mitogen Activated Protein Kinase (MAPK) inhibitors as co-treatments for radiation therapy is investigated, with special focus on a potential link between the MAPK pathway and tumor hypoxia, which is a critical determinant for response to therapy.

Materials And Methods: The effects of two MAPK inhibitors, Sorafenib and PD0325901, were monitored daily using in vivo EPR (Electron Paramagnetic Resonance) oximetry in FSaII and TLT tumor models in order to identify a window of reoxygenation, during which tumor blood flow, oxygen consumption and radiation sensitivity were assessed.

Results: Reoxygenation was shown after two days of treatments with Sorafenib or PD0325901 in two tumor models, which was further successfully exploited with Sorafenib for improving the radiation response of FSaII tumors by a factor of 1.