Antitumour Properties (antitumour + property)

Distribution by Scientific Domains


Selected Abstracts


Di- n -butyltin(IV) derivatives of bis(carboxymethyl)benzylamines: synthesis, NMR and X-ray structure characterization and in vitro antitumour properties

APPLIED ORGANOMETALLIC CHEMISTRY, Issue 7 2001
Teresa Mancilla
Abstract Four di- n -butyltin(IV) derivatives of bis(carboxymethyl)benzylamines were synthesized and their structure characterized by 1H,13C and ­117/119Sn NMR, Mössbauer spectroscopy and mass spectrometry. The derivative substituted in the meta position by a methyl group has been further characterized by X-ray crystallography. This compound exhibits a distorted trigonal bipyramidal geometry at tin. The NMR data in solution, as well as other spectroscopic results in the solid state, confirm this structure for all the compounds. Evidence is provided to show that the compounds are more highly associated in concentrated solution than in the solid state. Their in vitro antitumour activity is reported. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Effect of Bupleuri Radix Extracts on the Toxicity of 5-Fluorouracil in HepG2 Hepatoma Cells and Normal Human Lymphocytes

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008
Su Jin Kang
We sought to assess whether Bupleuri Radix extract enhances 5-fluorouracil-induced cytotoxicity in HepG2 hepatoma cells, while protecting normal blood lymphocytes. Bupleuri Radix, used for treatment of liver disease in oriental medicine, possesses antitumour properties; it induces apoptosis through cell arrest in tumour cells, but does not affect normal lymphocytes. In this study, we evaluated the protective and enhancing effects of Bupleuri Radix on 5-fluorouracil-induced cytotoxicity in HepG2 cells and normal lymphocytes. Treatment with Bupleuri Radix increased the micronuclei frequency and DNA damage, resulting from 5-fluorouracil treatment. However, when human lymphocytes were cotreated with Bupleuri Radix and 5-fluorouracil, the frequency of 5-fluorouracil-induced micronuclei decreased. Although the extent of 5-fluorouracil-induced DNA damage, determined by single-cell gel electrophoresis, increased after treating HepG2 cells with Bupleuri Radix, it decreased in normal lymphocytes. When cells were treated with 20 µM 5-fluorouracil and 200 µg/ml Bupleuri Radix simultaneously, Bax protein increased in HepG2 cells at 24 hr; however, p21 and p53 proteins were up-regulated in normal human lymphocytes. Cotreatment with 200 µg/ml Bupleuri Radix and 20 µM 5-fluorouracil resulted in cell arrest at the late G1/early S phase in HepG2 cells (55.80 ± 0.19%) and normal lymphocytes (97.19 ± 0.27%). In addition, Bupleuri Radix and 5-fluorouracil treatment increased mitochondria membrane potential collapse only in HepG2 cells (19.02%), while it was not changed in lymphocytes. In conclusion, our findings suggest that Bupleuri Radix may be effective as a therapeutic agent to treat hepatomas. [source]


Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2007
M Kobori
Background and purpose: 5,,8,-Epidioxy-22E -ergosta-6, 22-dien-3,-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol peroxide. Experimental approach: After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS-induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT-PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells. Key results: Ergosterol peroxide suppressed LPS-induced TNF-, secretion and IL-1,/, expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS-induced DNA binding activity of NF-,B and C/EBP,, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down-regulated the expression of low-density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG-CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress-inducible genes, and the cyclin-dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon-inducible genes. Conclusion and Implication: Our results suggest that ergosterol peroxide and ergosterol suppress LPS-induced inflammatory responses through inhibition of NF-,B and C/EBP, transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells. British Journal of Pharmacology (2007) 150, 209,219. doi:10.1038/sj.bjp.0706972 [source]


Disulfide Bond Substitution by Directed Evolution in an Engineered Binding Protein

CHEMBIOCHEM, Issue 8 2009
Antoine Drevelle Dr.
Abstract Breaking ties: The antitumour protein, neocarzinostatin (NCS), is one of the few drug-carrying proteins used in human therapeutics. However, the presence of disulfide bonds limits this protein's potential development for many applications. This study describes a generic directed-evolution approach starting from NCS-3.24 (shown in the figure complexed with two testosterone molecules) to engineer stable disulfide-free NCS variants suitable for a variety of purposes, including intracellular applications. The chromoprotein neocarzinostatin (NCS) has been intensively studied for its antitumour properties. It has recently been redesigned as a potential drug-carrying scaffold. A potential limit of this protein scaffold, especially for intracellular applications, is the presence of disulfide bonds. The objective of this work was to create a disulfide-free NCS-derived scaffold. A generic targeted approach was developed by using directed evolution methods. As a starting point we used a previously engineered NCS variant in which a hapten binding site had been created. A library was then generated in which cysteine Cys88 and Cys93 and neighbouring residues were randomly substituted. Variants that preserved the hapten binding function were selected by phage display and further screened by colony filtration methods. Several sequences with common features emerged from this process. The corresponding proteins were expressed, purified and their biophysical properties characterised. How these selected sequences rescued folding ability and stability of the disulfide-free protein was carefully examined by using calorimetry and the results were interpreted with molecular simulation techniques. [source]