Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects ...of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female Sprague-Dawley rats after the nocturnal administration of RES. Application of a high dose of RES (100 mg/kg body weight), starting 2 weeks before the first N-methyl-N-nitrosourea dose (NMU) (50 mg/kg body weight), reduced tumor incidence and markedly prolonged latency period (P < 0.01) in the NMU + RES group in comparison to NMU tumor bearing animals. In addition, the tumor volume decreased significantly (P < 0.05) together with tumor frequency (P < 0.05). We also observed that food but not water intake was significantly reduced by 17% between weeks 4 and 12 in the NMU + RES group leading to a pronounced reduction in the body mass of about 25% as compared to untreated controls. In addition to direct effects of RES in tumor tissues, this polyphenol did also improve metabolic functions in RES-treated animals since it normalizes hypoproteinemia and urea levels and increases the number of lymphocytes when compared with NMU. Higher level of reactive oxygen species (ROS) in leukocytes and the elevation of proinflammatory plasma cytokines IL-1 and IL-2 may contribute to the observed reduction in tumor development. These results indicate for the first time that nocturnal administration of a high dose of RES significantly affects tumor development in vivo. Therefore, we conclude that RES is a promising candidate for cancer chemoprevention. However, it should be noted that the mode of application might significantly affect RES ability to fight cancer.
Different species from the
Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary disorders in traditional European medicine. In this work, a fraction enriched in ...dicaffeoylquinic acids (DCCAs) and luteolin-7-
O-
β-
d-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic compound of
Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and luteolin-7-
O-
β-
d-glucuronide was prepared by solid phase extraction from a 20% methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-
O-
β-
d-glucuronide was determined by HPLC analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow (23–44–47%) by the
Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined effect of DCCAs and luteolin-7-
O-
β-
d-glucuronide stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they seem to be the choleretic active principles in the traditional application forms of yarrow.
The investigation of stable and radiogenic isotopes and of platinum-group (PGE) and rare earth elements (REE) in chromitites and associated ultramafic rocks of the Kempirsai Massif, southern Urals, ...gives strong evidence for a multistage formation of giant ophiolitic-podiform chromite deposits present in the southeastern part of the massif. The Kempirsai ophiolite massif is divided by a shear zone into two parts: in the northwestern area, small bodies of Al-rich chromite formed from basaltic melts between 420 to 400Ma, according to Sm-Nd mineral isochrons of harzburgite, pyroxenite, websterite and gabbro. Harzburgites and pyroxenites in this area are enriched in light REE and have ^sub Nd^(400)>+6 and ^sub Sr^(400)+5. Chromitites have scattered PGE distributions (Pd/Ir, 0.4-7.0), being partly enriched in Pd and Pt. γ^sub Os^(400) of one chromitite is -4.4. The southeastern part of the Kempirsai Massif, well-known for its world-class deposits of podiform low-Al magnesiochromite, is characterized by harzburgite and dunite enriched in light REE with very low ^sub Nd^(400) (+4.3 to -17.1) and positive ^sub Sr^(400) (>+10) values. Chromitites are strongly enriched in Ir, Os and Ru and depleted in Pd and Pt. γ^sub Os^(400) of three chromitites is uniform and approaches C1 and DMM compositions. In veins and pods postdating crystallization of massive chromite, pargasitic amphibole formed in equilibrium with fluid-inclusion-bearing chromite at temperatures close to 1000°C. These amphiboles give ^sup 40^Ar/^sup 39^Ar stepwise heating ages of 365 to 385Ma and are characterized by low ^sub Nd^(400) (+0.6 to -4.6) and general enrichment in REE. The cooling ages correspond to a 379.3±1.6Ma Rb-Sr mineral isochron produced from amphibole and phlogopite of a pyroxenite vein in the western part of the massif. From these data it is concluded that parts of the Kempirsai Massif have been pervasively metasomatized by large amounts of fluids and melts derived from a subducted slab composed of oceanic crust and sediments. Subduction occurred at least 15-35Ma after a melting event that produced a typical ophiolitic sequence in the Paleozoic Sakmara Zone. We conclude that large chromite orebodies formed from second-stage high-Mg melts that interacted with depleted mantle and fluids on their way upward in a suprasubduction zone regime, and in a fore-arc position to the Magnitogorsk island arc.PUBLICATION ABSTRACT
Melatonin exerts anti-proliferative and pro-apoptotic effects in various cancer cell lines. Furthermore, there is evidence for impaired melatonin secretion in human breast and colorectal cancer. ...Additionally, several studies revealed a modulated expression of the melatonin receptor 1 (MT1), in human breast cancer specimens. Since melatonin binding sites were already identified in the human intestine, our aim is to identify the expression and to characterize the localization of the MT1 receptor in the human colon and in particular to compare MT1 expression levels between non-malignant and malignant colonic tissue. We assessed MT1 transcript levels with real time RT-PCR in colon adenocarcinomas and the adjacent normal colonic mucosa of 39 patients and observed a significant decrease of MT1 mRNA expression in colorectal cancer compared with the healthy adjacent mucosa tissue (0.67 mean difference, P < 0.0001). The results were confirmed at the protein level by Western blot analysis and by immunohistochemistry. MT1 was localized mainly supranuclear in colonic epithelial cells lining the crypts. We also evaluated mRNA expression of different clock genes in the colon samples and found a significant correlation between MT1 and Cryptochrome 1 (Cry1) expression (P < 0.01 for normal and P < 0.05 for tumour tissue). In conclusion, the decreased expression of MT1 in human colorectal cancer could point to a role of melatonin in this disease.
Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with anticancer and cardioprotective activities, was studied in human liver cytosol. In the presence of ...3′-phosphoadenosine-5′-phosphosulfate, three metabolites (M1-3) whose structures were identified by mass spectrometry and NMR as trans-resveratrol-3-O-sulfate, trans-resveratrol-4′-O-sulfate, and trans-resveratrol-3-O-4′-O-disulfate, respectively. The kinetics of M1 formation in human liver cytosol exhibited an pattern of substrate inhibition with a Ki of 21.3 ± 8.73 µM and a Vmax/Km of 1.63 ± 0.41 µL min−1mg−1 protein. Formation of M2 and M3 showed sigmoidal kinetics with about 56-fold higher Vmax/Km values for M3 than for M2 (2.23 ± 0.14 and 0.04 ± 0.01 µL min−1 mg−1). Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. In conclusion, the results elucidate the enzymatic pathways of resveratrol in human liver, which must be considered in humans following oral uptake of dietary resveratrol.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
: Activation of the G‐protein‐coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells ...positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue‐Quest® software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER‐2 status. Nestin was located together with MT1 in myoepithelial cells in 38 NCa specimens (total n = 42) and in 18 Ca specimens with intact milk ducts. Quantitative evaluation of selected 16 NCa and Ca samples revealed that MT1 levels were higher in invasive Ca sections than in NCa specimens in eight and lower in six cases. Specimens from higher tumor stages (TII/III) with a higher risk of relapse were associated with MT1/nestin co‐staining in more than 10% of tumor cells, whereas a lack of co‐staining correlated with lower tumor stages. Abundant expression of MT1 and, particularly, coexpression of MT1 with nestin in invading tumor cells in more advanced tumors suggest an important role for this GPCR in the pathogenesis of breast cancer.
