Ole Vang

Roskilde University · Department of Science and Environment (DSE)

Tumor-associated macrophages (TAMs) support tumor growth by suppressing the activity of tumor-infiltrating T cells. Consistently, TAMs are considered a major limitation for the efficacy of cancer immunotherapy. However, the molecular reason behind the acquisition of an immunosuppressive TAM phenotype is not fully clarified. During tumor growth, the...

Usnic acid has anti-cancer activity, however, low solubility and toxicity limit the potential. To investigate biological activity of usnic acid derivatives, enantiopure derivatives were synthesised by reacting usnic acid with ethylenediamine, which yielded one dimer product ((+)-1), and two tetra cyclic compounds ((+)-2 and (-)-2). The products wer...

Throughout this book the power of combination chemoprevention is highlighted. Even individual agents that function by virtue of pleiotropic mechanisms of action portray a combination effect. In this final chapter, we offer a brief perspective on the concept of combining numerous (e.g., 10–25) dietary agents for the creation of a cocktail capable of...

This book discusses the efficacy of various naturally occurring chemopreventive agents in preventing or delaying cancer. It focuses on the holistic chemopreventive concept, demonstrating the relevant response is the combined effect of a series of compounds that alone have been shown to have some effect in different experimental models. Written by...

Background: Tumor-associated macrophages (TAMs) are known to support tumor growth by suppressing the activity of tumor infiltrating T cells. Consequently, the number of TAMs has been correlated with a poor prognosis of cancer. However, the molecular reason why TAMs acquire an immunosuppressive phenotype is still not completely understood. During so...

Table S3. Gene Expression in Nonmalignant Stromal Cells from Brain Metastatic Lesions

We synthesized a mitochondria-targeted honokiol (Mito-HNK) that facilitates its mitochondrial accumulation; this dramatically increases its potency and efficacy against highly metastatic lung cancer lines in vitro, and in orthotopic lung tumor xenografts and brain metastases in vivo. Mito-HNK is >100-fold more potent than HNK in inhibiting cell pro...

Resveratrol is a well-known phenolic stilbene because of its presence in several edible plants and its proposed properties that are beneficial to human health [...]

Resveratrol (Resv) is a polyphenol reported to modulate mitochondrial activity. The aim was to use HeLa and 143B cells to characterize the action of Resv on mitochondrial activity, cell size and proliferation using wild type (WT) and Rho 0 cells deficient in mitochondrial DNA. In both HeLa WT and Rho 0 cells, the oxygen consumption rate (OCR) was i...

Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. In insulinoma β-cells (INS-1E), Resv is previously shown to imp...

The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating the biological effects of...

Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR p...

Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized...

Testing the biological activities of a dietary compound like resveratrol presents various challenges, which are highlighted in this commentary, with some suggested direction for future research, focusing on five challenges: (1) many different cellular effects are observed for resveratrol, but it is not known whether they arise from one point of act...

Resveratrol (RSV) is a natural polyphenol produced by plants and is proposed to have multiple beneficial effects on health. In recent years, the interest in this molecule has increased nearly exponentially following the major findings that RSV (I) is chemo-preventive in some cancer models, (II) is cardio-protective and (III) has positive effects on...

Numerous scientific papers have suggested health-promoting effects of resveratrol, including claims in the prevention of diseases such as coronary heart disease, diabetes, and cancer. Therefore, it was proposed that the scientific community needed to express recommendations on the human use of resveratrol. Such recommendations were formulated after...

Rapamycin extends lifespan in mice, but can have a number of undesirable effects that may ultimately limit its utility in humans. The canonical target of rapamycin, and the one thought to account for its effects on lifespan, is the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). We have previously shown that at least some of the detr...

Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer...

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints with the potential to cause joint destruction and functional disability. While the effects can be seen in many tissues and organs, attacks are primarily against the synovial joints. Resveratrol, a phytoalexin found in grape skins and...

ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins, holds great promise to complement current cancer therapies. However many types of solid cancer cells are resistant to ABT-737. One practical approach to improve its therapeutic efficacy is to combine with the agents that can overcome such resistance to restore the sensitivity. In t...

Basic science literature abounds with molecules that promise to ameliorate almost any disease, from curing cancer to slowing the aging process itself. However, most of these compounds will never even be evaluated in humans, let alone proven effective. Here, we use resveratrol as an example to highlight the enormous difficulties in understanding pha...

Overview of the neuroprotective effect by resveratrol was in focus of 163 papers, of which 40 papers concerned animal with acute exposure and sub- and chronic exposure. The search terms “resveratrol” was used in combination with “neuroprotection” or “neuroprotective” including papers published up to September 2010. (DOCX)

Overview of experiments focusing on the effect of resveratrol on obesity and diabetes in experimental animals. In total, 218 articles were identified, but only 19 animal studies were found to investigate the non-acute effects of resveratrol. The search terms “resveratrol” were used in combination with “metabolic syndrome”, “obesity”, “diabetes”, “i...

Overview of the effect of resveratrol on cancer development in experimental animals. To identify papers investigating the cancer preventive potential of resveratrol, a literature search using the terms “resveratrol” in combination with “cancer”, “carcinogenesis” or “chemoprevention” up to September 2010 was performed. In total, 1191 papers were ide...

Overview of the effect of resveratrol on coronary heart disease models in experimental animals. To identify papers investigating the effect of resveratrol on coronary heart diseases, a literature search using the terms “resveratrol” in combination with “hypertension”, “heart failure”, “myocardial infarct”, “cardiac arrest”, “ischemia heart disease”...

Overview of the effect of resveratrol on inflammatory markers in experimental animals. To identify papers investigating the effect of resveratrol on inflammatory markers, a literature search using the terms “resveratrol” in combination with “inflammation” or “inflammatory” was done, including papers published up to September 2010. In total, 559 pap...

Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are ne...

RESUME Efterspørgslen på dermatologiske urte-og planteprodukter er steget gennem de seneste år, heriblandt også på produkter, der indeholder kamille. Ekstrakter og afkog af denne plante anbefa-les ofte af laegfolk til behandling af en raekke hudsygdomme som f.eks. betaendelse, sår og kløe. I denne oversigtsartikel be-skriver vi på baggrund af en sy...

Recent years have seen a rise in the demand for dermatological herbal and plant products as well as products containing chamomile. Extracts and decoctions made from this plant are often recommended by laymen for treatment of a number of skin diseases e.g. inflammation, wounds and itching. This systematic review explores the evidence base of the der...

A new geranylated coumarin, (E)-4-(1-hydroxypropyl)-5,7-dihydroxy-6-(3,7-dimethyl-2,6-octadienyl)-8-(3-methyl-1-oxobutyl)coumarin (named surangin D), was isolated from the bark of Mammea siamensis collected in Vietnam, along with four known coumarins, surangins B and C, and theraphins B and C, and seven xanthones, 1,7-dihydroxyxanthone, 7-hydroxy-1...

A new geranylated coumarin, (E)-4-(1-hydroxypropyl)-5,7-dihydroxy-6-(3,7-dimethyl-2,6-octadienyl)-8-(3-methyl-1-oxobutyl)coumarin (named surangin D), was isolated from the bark of Mammea siamensis collected in Vietnam, along with four known coumarins, surangins B and C, and theraphins B and C, and seven xanthones, 1,7-dihydroxyxanthone, 7-hydroxy-1...

Consumption of cruciferous vegetables and cancer prevention seem to be positively associated. We present an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human colon cancer cells DLD-1 and HCT 116 with IC(50) values...

Amyloid -peptide (A) and Paraquat PQ induce oxidative stress in astrocytes by formation of reactive oxygen species (ROS). The present study determines the cellular response to oxidative stress by use of proton nuclear magnetic resonance (1 H-NMR) spectroscopy. The cellular response was studied in cultured primary astrocytes exposed directly to 5 mM...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Two new geranylated xanthones, 6-O-methylcowanin (4) and oliverixanthone (5), along with five known compounds, cowanin, rubraxanthone, cowaxanthone, cowanol, and beta-mangostin, have been isolated from the bark of Garcinia oliveri. For comparison of their biological activities, one mono- and seven di-O-alkylated alpha-mangostin derivatives were syn...

Five crude extracts were made from leaves and stems of Jasminum subtriplinerve Blume (Oleaceae) and investigated for antimicrobial, antioxidant and cytotoxic activities. The extractions were done with petroleum ether, ethyl acetate, ethanol, methanol or water. All extracts exhibited anti-bacterial activity except the water fraction. On the other ha...

In the central nervous system oxidative stress has been implicated in the pathology of several neurological disorders. The ability to withstand reactive oxygen species and oxidative stress are essential for survival and therefore all aerobic cells are endowed with chemical and enzymatic antioxidative defense systems. The purpose of the present stud...

Resveratrol, a naturally occurring compound of various fruits such as grapes, is thought to possess chemopreventive properties. The levels of resveratrol in grapes and grape products including wine, varies from region to region and from one year to another. This paper reviews the resveratrol content in red wine based on relevant published data. Red...

Resveratrol, a phytochemical present in grapes, has been demonstrated to inhibit tumourigenesis in animal models. However, the specific mechanism by which resveratrol exerts its anticarcinogenic effect has yet to be elucidated. In the present study, the inhibitory effects of resveratrol on cell proliferation and apoptosis were evaluated in the huma...

Since the pioneer experiments of Wattenberg and co-workers in 1978 showing tumor inhibitory effects of various indoles (Wattenberg and Loub, 1978), great interest emerged in the anticarcinogenic properties of cruciferous vegetables and compounds therein. Evaluation of the available evidence on anticarcinogenic properties of cruciferous vegetables,...

(alpha)B-crystallin is a chaperone protein and a potential myelin antigen to human T cells in Multiple Sclerosis (MS). In this study we investigate the existence of (alpha)B-crystallin in the cerebrospinal fluid (CSF) of patients with clinical symptoms of MS and control individuals without these symptoms, using a newly developed (alpha)B-crystallin...

Recent results have shown that indole-3-carbinol (I3C) inhibits the cellular growth of human cancer cell lines. In some cruciferous vegetables, another indole, N-methoxyindole-3-carbinol (NI3C), is found beside I3C. Knowledge about the biological effects of NI3C is limited. The aim of the present study was to show the effect of NI3C on cell growth...

Indole-3-carbinol (I3C) is a naturally occurring substance that shows anti-carcinogenic properties in animal models. Besides its clear anti-carcinogenic effects, some studies indicate that I3C may sometimes act as a tumor promoter. Indolo[3,2-b]carbazole (ICZ), which is formed in the acidic environment of the stomach after intake of I3C, has a simi...

Modulation of xenobiotic metabolism, including cytochrome P-450 (CYP) enzyme activities, due to dietary intakes of cruciferous vegetables, has been described in animals and humans, and the induction of CYP1A enzymes is suggested mainly to be related to the content of indolyl glucosinolates in these vegetables. The aim of the present study was to ev...

Dietary broccoli exposure modulates various cytochrome P-450 (CYP)-associated activities and antioxidant defense enzyme activities in liver, colon, and kidney of rats. We present an analysis by the partial least-square method (PLS) of the contribution of single glucosinolates in modulating xenobiotic metabolizing and antioxidant defense enzyme acti...

Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The...

The naturally occurring stilbene/alexin trans-resveratrol (trans-3,5, 4'-trihydroxystilbene) is a promising agent for the prevention of cancer. We investigated the effect of resveratrol on gap-junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells because inhibition of GJIC is an important mechanism of tumor promotion....

The well-documented reduction of cancer risk by high dietary cruciferous vegetable intake may in part be caused by modulation of cytochrome P-450 (CYP) expression and activity by indoles. The purpose of the present experiments was to study the mechanism of CYP 1A1 induction by N-methoxyindole-3-carbinol (NI3C) in cultured cells and to compare the C...

The effects of vegetables on the activities of various metabolizing enzymes in liver and intestine have been studied intensively, whereas studies on effects on testicular metabolizing enzymes are lacking. The present report is the first describing the effects of dietary broccoli on the activities of a number of xenobiotic metabolizing enzymes from...

Modulation of cytochrome P4501A1 (CYP1A1) activity is a mechanism whereby indoles present in cruciferous vegetables could affect the metabolism of xenobiotics. Ascorbigen (ASG) is the predominant indole formed during the degradation of glucobrassicin, although the mechanism by which ASG modulates CYP1A1 activity is not known. The major focus of thi...

Indole-3-ylcarbinol (13C) is formed during processing of cruciferous vegetables and is suggested to be one of the modulators of drug-metabolising enzymes. Indole-3-ylcarbinol is a far less efficient inducer of hepatic enzymes after parenteral than after oral administration, due to formation of active metabolites in the gastrointestinal tract. As in...

Various dietary substances modulate the xenobiotic metabolism and may thereby protect against toxicity and carcinogenicity of food toxins. The effects of pure indolyl glucosinolates, which are present in cruciferous vegetables, on induction of specific cytochrome P-450 (CYP) and glutathione S-transferase (GST) isoforms have not been studied previou...

Eighteen volunteers received 500 g fresh broccoli every day for 12 days after a 6-day period of standard diet. The activity of CYP1A2, CYP2E1 and the estrone 2 and 16alpha-hydroxylation were determined prior to and after the broccoli diet. The average activity of CYP1A2 and the average 2/16alpha-hydroxyestrone ratio were increased 19% (P < 0.0005)...

The anti-carcinogenic activity of dietary fruit and vegetables observed in several epidemiological and experimental animal studies is likely to be an effect of the combined exposure to a large number of substances acting together. This is plausible, as these compounds are present simultaneously in a diet containing vegetables and fruit. Further, so...

Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influence on specific cytochrome P450 enzymes (CYP) and phase II drug metabolizing enzymes in humans and rodents. Thus CYP enzymes are involved in transformation of procarcinogens, mutagens, steroid hormones and a large variety of other endogenous and exogeno...

Inhibition of gap junctional intercellular communication (GJIC) is a predictive short term test for tumor promoting activity. A new metabolic cooperation assay has been developed, which takes the cytochrome P-450 metabolism into account. In this assay the inhibitory activity of tobacco smoke condensates (CSC) and CSC fractions from high and low tar...

The role of metabolism of tumour promoters on the inhibition of intercellular communication was investigated in a modified V79 metabolic cooperation system. V79 cells, which stably express different rat cytochrome P450 enzymes (CYP1A1, CYP1A2 or CYP2B1), were used in the metabolic cooperation assay. The inhibitory effect on intercellular communicat...

The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are import...

: The biotransformation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) and the protein binding of PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied using microsomes from PCB-pretreated or untreated male rats of the strains, Wistar, Fischer and Sprague-Dawley. The microsomal monooxygenases, P450IA1 and IA2, which are impo...

Ingestion of broccoli or other cruciferous vegetables inhibits the induction of cancer by chemicals and modifies some cytochrome P-450 enzyme activities. The effect of dietary broccoli on the levels of P450IA and IIB mRNA and proteins in rat liver and colon has been studied. Rats were fed a ten percent broccoli diet for 7 days. The expression of th...

It is known that consumption of cruciferous vegetables protects against the chemical induction of cancer in many organs. It has been suggested that this protection is mediated through an effect on the cytochrome P450 monooxygenase system. This system is responsible for the activation of a number of chemical carcinogens to their ultimate forms. In t...