A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC500.12-0.23 μM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 μM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 μM (0.38 μg/mL) and 3.9 μM (1.52 μg/mL) after 24 and 48 h, respectively.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antifungální látky chemická syntéza chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Bacteria účinky léků MeSH
- furany chemická syntéza chemie farmakologie MeSH
- houby účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- proliferace buněk účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
SCOPE: The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries. METHODS AND RESULTS: Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. CONCLUSION: We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines.
- MeSH
- antigeny CD95 metabolismus MeSH
- apoptóza účinky léků MeSH
- brusnice s jedlými plody chemie metabolismus MeSH
- buněčné linie MeSH
- chemorezistence MeSH
- DNA metabolismus MeSH
- fosfatidylseriny metabolismus MeSH
- fosforylace účinky léků MeSH
- fragmentace DNA účinky léků MeSH
- kaspasa 3 metabolismus MeSH
- kaspasa 8 metabolismus MeSH
- kaspasa 9 metabolismus MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- nádory tračníku metabolismus patologie MeSH
- ovoce chemie metabolismus MeSH
- proantokyanidiny chemie izolace a purifikace toxicita MeSH
- protein TRAIL toxicita MeSH
- rostlinné extrakty chemie MeSH
- TRAIL receptory metabolismus MeSH
- Vaccinium vitis-idaea chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.
- MeSH
- antioxidancia aplikace a dávkování farmakologie MeSH
- glutathionperoxidasa metabolismus MeSH
- katalasa metabolismus MeSH
- krysa rodu rattus MeSH
- oxidační stres účinky léků MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
- rostlinné přípravky aplikace a dávkování farmakologie MeSH
- Vaccinium macrocarpon chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver.
- MeSH
- benzofenantridiny analýza MeSH
- dieta MeSH
- feces chemie MeSH
- isochinoliny analýza MeSH
- játra enzymologie účinky léků MeSH
- krevní obraz MeSH
- krmivo pro zvířata analýza toxicita MeSH
- krysa rodu rattus MeSH
- léky rostlinné čínské analýza toxicita MeSH
- oxidační stres účinky léků MeSH
- Papaveraceae chemie MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
- potravinářské přísady analýza toxicita MeSH
- přijímání potravy MeSH
- systém (enzymů) cytochromů P-450 analýza metabolismus MeSH
- tělesná hmotnost účinky léků MeSH
- tkáňová distribuce MeSH
- velikost orgánu účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: UV radiation from sunlight is a very potent environmental risk factor in the pathogenesis of skin cancer. Exposure to UV light, especially the UVA part, provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in exposed cells. Topical application of antioxidants is a successful strategy for protecting the skin against UV-caused oxidative damage. OBJECTIVE: In this study, silybin (SB) and 2,3-dehydrosilybin (DS) (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage. METHODS: Human keratinocytes HaCaT were used as an appropriate experimental in vitro model, to monitor the effects of SB and DS on cell viability, proliferation, intracellular ATP and GSH level, ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage. RESULTS: Application of the flavonolignans (1-50 micromol/l) led to an increase in cell viability of irradiated (20 J/cm(2)) HaCaT keratinocytes. SB and DS also suppressed intracellular ATP and GSH depletion, ROS production and peroxidation of membrane lipids. UVA-induced caspases-3 activity/activation was suppressed by treatment with SB and DS. Lower concentrations of both compounds (10 micromol/l) significantly reduced cellular DNA single strand break formation. CONCLUSION: Taken together, the results suggest that these flavonolignans suppress UVA-caused oxidative stress and may be useful in the treatment of UVA-induced skin damage.
- MeSH
- antioxidancia farmakologie terapeutické užití terapeutické užití MeSH
- financování organizované MeSH
- kaspasa 3 metabolismus MeSH
- keratinocyty účinky léků účinky záření MeSH
- kůže patologie účinky záření MeSH
- lidé MeSH
- ostropestřec mariánský MeSH
- oxidační stres účinky léků účinky záření účinky záření MeSH
- peroxidace lipidů účinky léků MeSH
- poškození DNA účinky léků MeSH
- proliferace buněk účinky léků MeSH
- radiační poranění prevence a kontrola MeSH
- radioprotektivní látky farmakologie terapeutické užití terapeutické užití MeSH
- reaktivní formy kyslíku metabolismus MeSH
- silymarin farmakologie terapeutické užití MeSH
- transformované buněčné linie MeSH
- ultrafialové záření škodlivé účinky MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
