Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study

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• 作者：Lisa Repsold ; Thandi Mqoco ; Elize Wolmarans ; Sandra Nkandeu…
• 关键词：Whole blood ; Morphology ; ESE ; 15 ; ol ; ESE ; 16 ; Anticancer ; Erythrocytes
• 刊名：Biological Research
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：47
• 期：1
• 全文大小：1125KB
• 参考文献：1.Stander A, Joubert F, Joubert A: Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs. Chem Biol Drug Des 2011,77(Suppl 3):173鈥?81.PubMed CrossRef
  2.Stander BA, Joubert F, Tu C, Sippel KH, McKenna R, Joubert AM: In vitro evaluation of ESE-15-ol, an estradiol analogue with nanomolar antimitotic and carbonic anhydrase inhibitory activity. PLoS One 2012,7(Suppl 12):e52205.PubMed CrossRef PubMed Central
  3.Stander BA, Joubert F, Tu C, Sippel KH, McKenna R, Joubert AM: Signaling pathways of ESE-16, an antimitotic and anticarbonic anhydrase estradiol analog, in breast cancer cells. PLoS One 2013,8(Suppl 1):e53853.PubMed CrossRef PubMed Central
  4.Chua YS, Chua YL, Hagen T: Structure activity analysis of 2-methoxyestradiol analogues reveals targeting of microtubules as the major mechanism of antiproliferative and proapoptotic activity. Mol Cancer Ther 2010,9(1):224鈥?35. 10.1158/1535-7163.MCT-09-1003PubMed CrossRef
  5.Voster CJJ, Joubert AM: In vitro effects of 2-methoxyestradiol-bis-sulphamate on the non-tumorigenic MCF-12A cell line. Cell Biochem Funct 2010, 28:412鈥?19. 10.1002/cbf.1671CrossRef
  6.Newman SP, Ireson CR, Tutill HJ, Day JM, Parsons MF, Leese MP, Potter BVL, Reed MJ, Purohit A: The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells. Cancer Res 2006,66(1):324鈥?30. 10.1158/0008-5472.CAN-05-2391PubMed CrossRef
  7.Liu Q, Jin W, Zhu Y, Zhou J, Lu M, Zhang Q: Synthesis of 3鈥?methoxy-E-diethylstilbestrol and its analogs as tumor angiogenesis inhibitors. Steroids 2012,77(5):419鈥?23. 10.1016/j.steroids.2011.12.024PubMed CrossRef
  8.Leese MP, Leblond B, Newman SP, Purohit A, Reed MJ, Potter BV: Anti-cancer activities of novel D-ring modified 2-substituted estrogen-3-O-sulfamates. J Steroid Biochem Mol Biol 2005, 94:239鈥?51. 10.1016/j.jsbmb.2005.01.005PubMed CrossRef
  9.Chander SK, Foster PA, Leese MP, Newman SP, Potter BV, Purohit A, Reed MJ: In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol. Br J Cancer 2007,96(9):1368鈥?376.PubMed PubMed Central
  10.Nkandeu DS, Mqoco TV, Visagie MH, Stander BA, Wolmarans E, Cronje MJ, Joubert AM: In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-beta-estradiol analogue in breast adenocarcinoma cells. Cell Biochem Funct 2013,31(Suppl 7):566鈥?74.PubMed
  11.Theron AE, Nolte EM, Lafanechere L, Joubert AM: Molecular crosstalk between apoptosis and autophagy indiced by a novel 2-methoxyestradiol analogue in cervical adenocarcinoma cells. Cancer Cell Int 2013, 13:87. 10.1186/1475-2867-13-87PubMed CrossRef PubMed Central
  12.Genis C, Sippel KH, Case N, Cao W, Avvaru BS, Tartaglia LJ, Govindasamy L, Tu C, Agbandje-McKenna M, Silverman DN, Rosser CJ, McKenna R: Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties. Biochemistry 2009,48(6):1322鈥?331. 10.1021/bi802035fPubMed CrossRef PubMed Central
  13.Thiry A, Dogne JM, Masereel B, Supuran CT: Targeting tumor-associated carbonic anhydrase IX in cancer therapy. Trends Pharmacol Sci 2006,27(11):566鈥?73. 10.1016/j.tips.2006.09.002PubMed CrossRef
  14.Benson EA, Skaar TC: Incubation of whole blood at room temperature does not alter plasma concentration of MicroRNA-16 and -223. Drug Metab Dispos 2013, 41:1778鈥?781. 10.1124/dmd.113.052357PubMed CrossRef
  15.Hess JR: Measures of stored red blood cell quality. Vox Sang 2014. doi:10.1111/vox.12130. [Epub ahead of print]
  16.Van der Meer PF, Cancelas JA, Cardigan R, Devine DV, Gulliksson H, Sparrow RL, Vassallo RR, de Wildt-Eggen J, Baumann-Baretti B, Hess JR: Evaluation of overnight hold of whole blood at room temperature before component processing: effect of red blood cell (RBC) additive solutions on in vitro RBC measures. Transfusion 2011, 51:15S-24S.PubMed CrossRef
  17.Pandey KB, Rizvi SI: Biomarkers of oxidative stress in red blood cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011,155(Suppl 2):131鈥?36.PubMed CrossRef
  18.Pretorius E: The adaptability of red blood cells. Cardiovasc Diabetol 2013,12(Suppl 1):63.PubMed CrossRef PubMed Central
  19.Baumgarten A, Wilhelmi M, Kalbantner K, Ganter M, Mischke R: Measurement of platelet aggregation in ovine blood using a new impedance aggregometer. Vet Clin Pathol 2010,39(Suppl 2):149鈥?56.PubMed
  20.Kloverpris H, Fomsgaard A, Handley A, Ackland J, Sullivan M, Goulder P: Dimethyl sulfoxide (DMSO) exposure to human peripheral blood mononuclear cells (PBMCs) abolish T cell responses only in high concentrations and following coincubation for more than two hours. J Immunol Methods 2010, 356:70鈥?8. 10.1016/j.jim.2010.01.014PubMed CrossRef
  21.Pretorius E, Bornman MS, Reif S, Oberholzer HM, Franz RC: Ultrastructural changes of platelet aggregates and fibrin networks in a patient with renal clear cell adenocarcinoma: a scanning electron microscopy study. Microsc Res Tech 2009,72(Suppl 9):679鈥?83.PubMed CrossRef
  22.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69鈥?0. 10.3322/caac.20107PubMed CrossRef
  23.Kamangar F, Dores GM, Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006,24(Suppl 14):2137鈥?150.PubMed CrossRef
  24.Dickens C, Joffe M, Jacobson J, Venter F, Sch眉z J, Cubasch H, McCormack V: Stage at breast cancer diagnosis and distance from diagnostic hospital in a periurban setting: A South African public hospital case series of over 1,000 women. Int J Cancer 2014. doi:10.1002/ijc.28861
  25.Pretorius E, Briedenhann S, Marx J, Smit E, Van Der Merwe C, Pieters M, Franz C: Ultrastructural comparison of the morphology of three different platelet and fibrin fiber preparations. Anat Rec 2007,290(Suppl 2):188鈥?98.CrossRef
  26.Evans BC, Nelson CE, Yu SS, Beavers KR, Kim AJ, Li H, Nelson HM, Giorgio TD, Duvall CL: Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J Vis Exp 2013,73(e50166):e50166. doi:10.3791/50166PubMed
  27.Tesoriere L, Butera D, Allegra M, Fazzari M, Livrea MA: Distribution of betalain pigments in red blood cells after consumption of cactus pear fruits and increased resistance of the cells to ex vivo induced oxidative hemolysis in humans. J Agric Food Chem 2005, 53:1266鈥?270. 10.1021/jf048134+PubMed CrossRef
  
• 作者单位：Lisa Repsold (4)
  Thandi Mqoco (4)
  Elize Wolmarans (4)
  Sandra Nkandeu (4)
  Joji Theron (4)
  Tomek Piorkowski (4)
  Peet du Toit (4)
  Dirk van Papendorp (4)
  Annie Margaretha Joubert (4)
  
  4. Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
  
• 刊物类别：Life Sciences, general; Cell Biology; Neurosciences; Developmental Biology; Microbiology; Plant Scie
• 刊物主题：Life Sciences, general; Cell Biology; Neurosciences; Developmental Biology; Microbiology; Plant Sciences;
• 出版者：BioMed Central
• ISSN：0717-6287

文摘

Background Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female鈥檚 erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22掳C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22掳C and 37掳C.