Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine oxidase was purified from bovine milk-fat globule membrane by extraction with butan-1-ol, precipitation with ammonium sulphate, separation by preparative electrofocusing and chromatography on Concanavalin-A/Agarose. The enzyme had an A280/A450 ratio of 4.8 and a specific activity of 3.09. At least five to seven variants of the enzyme with isoelectric points from pH 6.9 to 7.6 were identified. Previously identified minor "variants' of the enzymes with apparently acidic isoelectric points (1) were shown to be the result of aggregation of enzyme with membrane sialoglycoproteins. Specific antibodies to xanthine oxidase were prepared by fractionating immune serum on a column of enzyme covalently bound to Sepharose 4B. A single immunoprecipitate was obtained when the purified antibodies were allowed to diffuse in agarose gels against either Triton-X-100-extracted membrane or purified xanthine oxidase. Immunoelectrophoresis of the enzyme against anti-sera to xanthine oxidase, however, revealed two precipitin lines, both of which were positive when histochemically stained for enzyme activity. The results are discussed with reference to previous purification schemes for xanthine oxidase and previous estimates for the isoelectric points of the enzyme. We also outline practical uses for the antibody prepared against the enzyme in this present study.
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PMID:Purification of xanthine oxidase from the fat-globule membrane of bovine milk by electrofocusing. 689 60

Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide, SR 4233) is the lead compound of a new class of hypoxic cell cytotoxins showing considerable antitumor activity. Hypoxic cytotoxicity of tirapazamine is believed to be mediated by free radical attack of its one-electron reduced metabolite on DNA, but little is known about the DNA lesions induced by the drug. Using the anoxic xanthine/xanthine oxidase system to effect one-electron reduction of tirapazamine under controlled conditions, we studied the action of the drug toward pUC18 and calf thymus DNA. Agarose gel electrophoresis indicated that tirapazamine causes substantially higher levels of single-strand breakage than double-stand breakage. The 5' DNA termini at the single-strand breaks were shown to be phosphorylated. Little, if any, base damage was observed when the damaged DNA was analyzed by a 32P-postlabeling assay. The major detectable lesion (comprising approximately 32% of the 3' ends of tirapazamine-induced single-strand breaks) was the phosphoglycolate moiety, which is caused by deoxyribose fragmentation. Since phosphoglycolate formation requires the addition of oxygen, we conclude that tirapazamine acts in a dual fashion to produce phosphoglycolates: (a) to generate a free radical in the deoxyribose ring (i.e., .C-4' and (b) then to donate an oxygen atom. The oxygen donation by tirapazamine was confirmed by anoxic irradiation of DNA in the presence of the unmetabolized drug. Increasing the concentration of the drug (up to 50 microM) led to a dramatic increase in the yield of phosphoglycolate.
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PMID:Dual action of tirapazamine in the induction of DNA strand breaks. 860 6

A total of 14 poly-herbal formula extracts were compared for their biological activities both in vivo and in vitro. Pretreatment of mice with the extracts protected them from E. coli infection to various extents. Among the extracts, the HD-12 and DLH-3073 extracts showed the highest cytotoxicity against both HIV-infected and mock-infected MT4 cells, without induction of any apparent anti-HIV activity. The extracts showed significantly higher cytotoxic activity against five human tumor cell lines (HSC-2, HSC-3, HSG, MT-4, HL-60) than against three normal human cell lines (HGF, HPC, HPLF). Agarose gel electrophoresis demonstrated that the HD-12 and DLH-3073 extracts induced intemucleosomal DNA fragmentation in HL-60 cells. ESR spectroscopy showed that all the extracts produced radicals and this was paralleled by their ability to scavenge the superoxide anion (produced by hypoxanthine-xanthine oxidase reaction), the hydroxyl radical (produced by Fenton reaction) and nitric oxide (produced by NOC- 7) in the presence of radical trapping agents. Higher and lower concentrations of extracts enhanced or reduced respectively, the radical intensity of sodium ascorbate, suggesting their bimodal actions. The tumor specificity and antioxidant properties of the herb extracts further suggest their medicinal efficacy.
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PMID:Tumor-specificity and radical scavenging activity of poly-herbal formula. 1216 29

A total of 6 newly-synthesized styrylchromones (SC-1 approximately SC-6) were compared for their cytotoxic activity against three normal oral human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF) and four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60). All compounds showed higher cytotoxic activity against tumor cell lines than against normal cells. Among the 6 compounds, SC-3, SC-4 and SC-5, which have one to three methoxy groups, showed higher tumor specificity and water solubility. The cytotoxic activity of SC-3 and SC-5 was slightly reduced by a lower concentration of NADH, a quinone reductase, but that of SC-3 was enhanced by higher concentrations of NADH, possibly due to demethylation of the methoxy groups. Agarose gel electrophoresis demonstrated that SC-3 and SC-5 induced intemucleosomal DNA fragmentation in HL-60 cells and production of large DNA fragment in HSC-2 cells. Both SC-3 and SC-5 enhanced the enzymatic activity to cleave the substrates for caspases 3, 8 and 9, suggesting the activation of both extrinsic and intrinsic apoptosis pathways. ESR spectroscopy showed that these compounds produced no detectable amount of radical and did not scavenge superoxide anion generated by the hypoxanthine-xanthine oxidase reaction. The highly tumor-specific cytotoxic action and apoptosis-inducing capability of SC-3 and SC-5 suggest their applicability for cancer chemotherapy.
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PMID:Cytotoxic activity of styrylchromones against human tumor cell lines. 1579 68