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JA Ochoa-Alvarez H Krishnan Y Shen NK Acharya M Han DE McNulty H Hasegawa T Hyodo T Senga JG Geng M Kosciuk SS Shin JS Goydos D Temiakov RG Nagele GS Goldberg 《PloS one》2012,7(7):e41845
Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors that have not been identified. We report here that a lectin from the seeds of Maackia amurensis (MASL) with affinity for O-linked carbohydrate chains containing sialic acid targets PDPN to inhibit transformed cell growth and motility at nanomolar concentrations. Interestingly, the biological activity of this lectin survives gastrointestinal proteolysis and enters the cardiovascular system to inhibit melanoma cell growth, migration, and tumorigenesis. These studies demonstrate how lectins may be used to help develop dietary agents that target specific receptors to combat malignant cell growth. 相似文献
23.
D Taruscio C Morciano P Laricchiuta P Mincarone F Palazzo CG Leo S Sabina R Guarino J Auld T Sejersen D Gavhed K Ritchie M Hilton-Boon J Manson PG Kanavos D Tordrup V Tzouma Y Le Cam J Senecat G Filippini S Minozzi C Del Giovane H Schünemann JJ Meerpohl B Prediger L Schell R Stefanov G Iskrov T Miteva-Katrandzhieva P Serrano-Aguilar L Perestelo-Perez MM Trujillo-Martín J Pérez-Ramos A Rivero-Santana A Brand H van Kranen K Bushby A Atalaia J Ramet L Siderius M Posada I Abaitua-Borda V Alonso Ferreira M Hens-Pérez FJ Manzanares 《Orphanet journal of rare diseases》2014,9(Z1):O14
24.
Carly Griffin Natasha Sharda Divya Sood Jerald Nair James McNulty Siyaram Pandey 《Cancer cell international》2007,7(1):10
Background
Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton. 相似文献25.
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McNulty PH King N Scott S Hartman G McCann J Kozak M Chambers CE Demers LM Sinoway LI 《American journal of physiology. Heart and circulatory physiology》2005,288(3):H1057-H1062
Patients with heart disease are frequently treated with supplemental oxygen. Although oxygen can exhibit vasoactive properties in many vascular beds, its effects on the coronary circulation have not been fully characterized. To examine whether supplemental oxygen administration affects coronary blood flow (CBF) in a clinical setting, we measured in 18 patients with stable coronary heart disease the effects of breathing 100% oxygen by face mask for 15 min on CBF (via coronary Doppler flow wire), conduit coronary diameter, CBF response to intracoronary infusion of the endothelium-dependent dilator ACh and to the endothelium-independent dilator adenosine, as well as arterial and coronary venous concentrations of the nitric oxide (NO) metabolites nitrotyrosine, NO(2)(-), and NO(3)(-). Relative to breathing room air, breathing of 100% oxygen increased coronary resistance by approximately 40%, decreased CBF by approximately 30%, increased the appearance of nitrotyrosine in coronary venous plasma, and significantly blunted the CBF response to ACh. Oxygen breathing elicited these changes without affecting the diameter of large-conduit coronary arteries, coronary venous concentrations of NO(2)(-) and NO(3)(-), or the coronary vasodilator response to adenosine. Administering supplemental oxygen to patients undergoing cardiac catheterization substantially increases coronary vascular resistance by a mechanism that may involve oxidative quenching of NO within the coronary microcirculation. 相似文献
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McLachlan A Kekre N McNulty J Pandey S 《Apoptosis : an international journal on programmed cell death》2005,10(3):619-630
The major hurdle in the fight against cancer is the non-specific nature of current treatments. The search for specific drugs that are non-cytotoxic to normal cells and can effectively target cancer cells has lead some researchers to investigate the potential anti-cancer activity of natural compounds. Some natural compounds, such as Taxol, have been shown to posses some anti-cancer potential. Pancratistatin (PST) is a natural compound that was isolated from the spider lily Pancratium littorale and shown to exhibit antineoplastic activity. The specificity of PST to cancer cells and the mechanism of PSTs action remain unknown. This study provides a detailed look at the effect of PST treatment on cancerous and normal cells. Our results indicate that PST induced apoptosis selectively in cancer cells and that the mitochondria may be the site of action of PST in cancer cells. A biochemical target available specifically in cancer cells may lead to the development of new and more effective cancer fighting agents. 相似文献
29.
The synthesis of 3-deoxydihydrolycoricidine, a key element toward elucidation of the pancratistatin anticancer pharmacophore, is described. Biological evaluation of this compound showed it to be significantly less active against tumor cells than pancratistatin. In addition to those features previously identified, the requirement of a 2,3,4-triol functionalized ring-C is now definitely established as the minimum pharmacophoric element for potent anticancer activity. 相似文献
30.
White RA Boydston LA Brookshier TR McNulty SG Nsumu NN Brewer BP Blackmore K 《Genomics》2005,86(6):668-673
Defects in iron absorption and utilization lead to iron deficiency and anemia. While iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. We undertook a positional cloning project to identify the causative mutation for the hemoglobin-deficit (hbd) mouse mutant, which suffers from a microcytic, hypochromic anemia apparently due to defective iron transport in the endocytosis cycle. As shown by previous studies, reticulocyte iron accumulation in homozygous hbd/hbd mice is deficient despite normal binding of transferrin to its receptor and normal transferrin uptake in the cell. We have identified a strong candidate gene for hbd, Sec15l1, a homologue to yeast SEC15, which encodes a key protein in vesicle docking. The hbd mice have an exon deletion in Sec15l1, which is the first known mutation of a SEC gene homologue in mammals. 相似文献