An estrogen analogue and promising anticancer agent refrains from inducing morphological damage and reactive oxygen species generation in erythrocytes, fibrin and platelets: a pilot study

Cancer Cell International

Annie Margaretha Joubert¹  Etheresia Pretorius¹  Lisa Repsold¹ 

[1] Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

关键词: Cancer;    Reactive oxygen species;    5(10)16-tetraene;    3;    2-Ethyl-3-O-sulphamoyl-estra-1;    2-Methoxyestradiol analogues;   

Others  :  791891
DOI  :  10.1186/1475-2867-14-48

 received in 2014-03-28, accepted in 2014-05-26,  发布年份 2014

【 摘 要 】

Background

2-Methoxyestradiol is known to have antitumour and antiproliferative action in vitro and in vivo. However, when 2-methoxyestradiol is orally administered, it is rapidly oxidized by the enzyme 17β-hydroxysteriod dehydrogenase in the gastrointestinal tract. Therefore, 2-methoxyestradiol never reaches high enough concentrations in the tissue to be able to exert these antitumour properties. This resulted in the in silico-design of 2-methoxyestradiol analogues in collaboration with the Bioinformatics and Computational Biology Unit (UP) and subsequent synthesis by iThemba Pharmaceuticals (Pty) Ltd (Modderfontein, Midrand, South Africa). One such a novelty-designed analogue is 2-ethyl-3-O-sulphamoyl-estra-1, 3, 5(10)16-tetraene (ESE-16).

Methods

This pilot study aimed to determine the morphological effect and possible generation of reactive oxygen species by ESE-16 on erythrocytes and platelet samples (with and without added thrombin) by means of scanning electron microscopy, transmission electron microscopy and flow cytometry.

Results

Erythrocytes and platelets were exposed to ESE-16 at a concentration of 180nM for 24Â hours. Scanning- and transmission electron microscopy indicated that ESE-16 did not cause changes to erythrocytes, platelets or fibrin networks. Flow cytometry measurements of hydrogen peroxide and superoxide indicated that ESE-16 does not cause an increase in the generation of reactive oxygen species in these blood samples.

Conclusion

Further in vivo research is warranted to determine whether this novel in silico-designed analogue may impact on development of future chemotherapeutic agents and whether it could be considered as an antitumour agent.

【 授权许可】

   
2014 Repsold et al.; licensee BioMed Central Ltd.

【 图 表 】

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