Radiotherapy-induced toxicity is a major dose-limiting factor in anti-cancer treatment. Ionizing radiation leads to the formation of reactive oxygen and nitrogen species (ROS/RNS) that are associated with radiation-induced cell death. Investigations of biological effects of fullerenol have provided evidence for its ROS/RNS scavenger properties in vitro and radioprotective efficiency in vivo. Therefore we were interested to evaluate its radioprotective properties in vitro in the human erythroleukemia cell line. Pre-treatment of irradiated cells by fullerenol exerted statistically significant effects on cell numbers and the response of antioxidative enzymes to X-ray irradiation-induced oxidative stress in cells. Our study provides evidence that the pre-treatment with fullerenol enhanced the enzymatic activity of superoxide dismutase and glutathione peroxidase in irradiated K562 cells.
PURPOSE Due to a lack of chemotherapeutics to efficiently control neoplastic processes, there is a need for discovering new, more efficient anticancer drugs that would distinguish malignant from normal cells. MATERIALS AND METHODS We studied the effect of short (4 h) and long (72 h) treatment with different concentrations of the enzymatically synthesized lignin model compound (DHP) on the proliferation of two human cell lines grown in tissue culture: breast adenocarcinoma (MCF7) and normal fetal lung fibroblast (MRC5) cell lines. RESULTS The growth of both MRC5 and MCF7 cell lines was inhibited by DHP after 4 h-treatment, while the carcinoma cell line was also sensitive to the long-term treatment with lower dose of DHP in comparison with the fetal cells. The low molecular weight DHP fractions inhibited growth of the MRC5 cells at lower concentrations compared to the treatment with all DHP fractions. CONCLUSION The higher sensitivity to DHP of the human malignant cells compared to the normal transformed ones gives the possibility to further study DHP as a therapeutic agent.
The aromatic herb Melissa officinalis L. can be used as an easily accessible source of natural antioxidants and as a possible food supplement and as a phytochemical. Radical scavenging, antibacterial, and antiproliferative activities of petroleum ether, chloroform, ethyl acetate, n-butanol, and water extracts of M. officinalis L. extracts were investigated. The results of antioxidative activity, obtained by electron spin resonance spectroscopy, confirmed that investigated extracts suppressed the formation of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and lipid peroxyl radicals in all investigated systems in a dose-dependent manner. The maximum DPPH and hydroxyl radical scavenging activities (SA(DPPH) = SA(OH) = 100%) were achieved in the presence of n-butanol extract at concentrations of 0.4 mg/mL and 0.5 mg/mL, respectively. The highest lipid peroxyl scavenging activity (93.20%) was observed at a higher concentration (5 mg/mL) of n-butanol extract in the lipid peroxidation system. The most effective antibacterial activities were expressed by petroleum ether and ethyl acetate extracts on Sarcina lutea. Chloroform extract showed the strongest antiproliferative effect with 50% inhibitory concentration values of 0.09 mg/mL and 0.10 mg/mL for HeLa and MCF-7 cell lines, respectively. The present study demonstrated the high phenolic content and radical scavenging, antibacterial, and antiproliferative activities of extracts of M. officinalis L. originating from Serbia.
Background: A rapid increase in the turnover of malignant cells modulates the enzymes level in circulation and may be a prognostic sign of disease progression. We evaluated the activity of serum lactate dehydrogenase and superoxide dismutase in erythrocytes of breast cancer patients immediately after surgery and before adjuvant therapy. Methods: Fourteen newly operated breast cancer patients were included in the study. Lactate dehydrogenase and superoxide dismutase activity were estimated using standard tests for evaluation of enzyme activity. Results: Activity of lactate dehydrogenase was in normal range in all but one sample obtained from patient at clinical status IIIB. Superoxide dismutase activity was elevated in 11 out of 14 patients, and was 2 to 8 fold higher compare to control values. The highest activity of superoxide dismutase was found in samples of two patients at clinical status I. Conclusion: Determination of lactate dehydrogenase and superoxide dismutase activity might be useful in clinical follow up of breast cancer patients.
Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 2-11 were synthesized. Protection of the 17-oxo function of compound 1 with ethylene glycol yielded compounds 2 and 3. The Oppenauer oxidation of 2 or oxidation with H 2 O 2 in alkaline conditions gave the respective compounds 4 and 10. Epoxidation of compound 4 yielded a mixture of 4a,5a- and 4β,5β-epoxides 5 and 6 and a mixture of 4α,5α- and 4β,5β-epoxy-carboxamides 7 and 8. Opening of the oxirane ring of a mixture of compounds 5 and 6 with formic acid afforded the 4-hydroxy derivative 9. Anti-aromatase activity and in vitro cytotoxicity for three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer, PC3) of selected compounds were evaluated. Compounds 2, 4, 9, and 10 showed a strong cytotoxicity for PC3 cells.
This study was conducted with intention to reveal the quantitative values of feto-maternal nutrition exchange in smokers placentas, considering the great importance of harmful influence of smoking in pregnancy. The study was done on 90 human placentas. We have divided them into three groups: 30 placentas of moderate smokers, 30 placentas of heavy smokers and control group (non-smokers). Stereologic analysis was done with multipurpose test system M42. Pregnant smokers (both moderate and heavy) had significantly lower length density of the blood vessels compared to the control group. Significantly higher surface density of the blood vessels was found in the pregnant heavy smokers. The least absolute length density of the resorption villi's blood vessels was in the pregnant heavy smokers and it was significantly lower compared to pregnant moderate smokers and control group. In the group of the pregnant heavy smokers there was statistically higher average absolute surface of the blood vessels. The intensity of smoking effects the structural changes of the placenta. Intensity of smoking during pregnancy had a great impact on the proportion of the morphologic changes of the placentas. It leads to hypoxia, which in turn may be the cause of fetal growth and developmental retardation.
Chemical modification of fullerenes to hydrosoluble cluster molecules made fullerenes interesting for biological investigation. Among them, polycarbonated and polyhydroxylated fullerene C60 derivatives showed the most interesting biological activities. In this paper, we present the most important recent results of in vitro and in vivo biological studies with fullerenol C60(OH)24. Fullerenol C60(OH)24 was strong antioxidant: it reacted with superoxide anion radical, hydroxy radical and nitrous oxide radical in chemical and biological systems. Fullerenol C60(OH)24 did not inhibit human breast cancer cell growth at concentrations from 0.8 to 3.45 μM, but strongly modulated cytotoxic effects of doxorubicin and cis-platinum after 24 and 48 hours of treatment. Radioprotective effects of fullerenol C60(OH)24 were shown in different in vitro and in vivo models. Fullerenol C60(OH)24 (100 mg/kg) protected rat heart from doxorubicin toxicity. Biodistribution studies of fulelrenol were also investigated. Accumulating data from the literature and from our studies suggest that fullerenol, as a nanoparticle might be a new promising pharmaceutical in the near future.
A new divergent approach to (+)-goniofufurone (1) and 7-epi-(+)-goniofufurone (2), as well as the first total synthesis of crassalactone C (3), has been achieved starting from D-xylose. In a preliminary bioassay, all three natural products 1, 2, and 3 showed remarkable in vitro antiproliferative activities against K562, Raji, and HeLa neoplastic cell lines.
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