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Lisa Repsold

University of Pretoria, South Africa

Title: Ex vivo apoptotic, autophagic and angiogenic influence of an estradiol analogue on platelets

Biography

Biography: Lisa Repsold

Abstract

Platelets are known contributors to vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in the release of angiogenic activators thereby promoting angiogenesis. Angiogenesis-regulating proteins are ideal biomarkers in the study of cancer pathophysiology and represent desirable therapeutic- and diagnostic targets.

The in silico-designed analogue of 2-methoxyestradiol, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16), binds to carbonic anhydrase II delaying early metabolism and is thus carried into the circulation. The effect it potentiates on blood components, especially on platelets, is of significance in cancer progression. This study thus investigated the possible ex vivo apoptotic, autophagic and angiogenic effects of ESE-16 on platelets.

Scanning electron microscopy was used to assess morphological changes in platelets after exposure to ESE-16 and no changes were observed in ESE-16-treated platelets. The possible induction of apoptosis and autophagy was determined by annexin V-FITC, measurement of caspase 3 activity, autophagy-related protein 5 levels, light chain 3-I to light chain 3-II conversion and monodansylcadaverine staining which indicated that there was no increase in apoptosis or autophagy when platelets were exposed to ESE-16. The expression of the angiogenic proteins namely vascular endothelial growth factor, platelet derived growth factor and matrix metallopeptidase-9 was also assessed and results showed that levels were significantly increased after platelets were added to MCF-7 cells.

This is the first ex vivo study to highlight possible involvement of angiogenesis, apoptosis, autophagy in platelets after exposure to this potential anti-cancer compound warranting further investigation concerning these signaling pathway targets on platelets of cancer patients.