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Experimental Hematology & Oncology
Published in: Experimental Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

Ex vivo apoptotic and autophagic influence of an estradiol analogue on platelets

Authors: Lisa Repsold, Etheresia Pretorius, Annie Margaretha Joubert

Published in: Experimental Hematology & Oncology | Issue 1/2015

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Abstract

Background

Platelets are known contributors to the vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in degranulation and release of constituents. Since the apoptotic- and autophagic effects of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) has been shown to occur in vitro and this compound was designed to bind to carbonic anhydrase II (CAII), the possible occurrence of these cell death mechanisms in platelets as circulatory components, is of importance.

Methods

Scanning electron microscopy was used to assess morphological changes in platelets after exposure to ESE-16. The possible apoptotic- and autophagic effect of ESE-16 in platelets was also determined by means of flow cytometry through measurement of Annexin V-FITC, caspase 3 activity, autophagy related protein 5 levels and light chain 3-I to light chain 3-II conversion.

Results

Scanning electron microscopy revealed no changes in ESE-16-treated platelets when compared to vehicle-treated samples. Apoptosis detection by Annexin V-FITC and measurement of caspase 3 activity indicated that there was no increase in apoptosis when platelets were exposed to ESE-16. The incidence of autophagy by measurement of autophagy related protein 5 levels and light chain 3-I to light chain 3-II conversion showed that exposure to ESE-16 did not cause the incidence of autophagy in platelets.

Conclusion

This is the first ex vivo study reporting on involvement of apoptosis- and autophagy-related targets in platelets after exposure to ESE-16, warranting further investigation in platelets of cancer patients.
Literature
1.
Li J, Xia Y, Bertino AM, Coburn JP, Kuter DJ. The mechanism of apoptosis in human platelets during storage. Transfusion. 2000;40(11):1320–9.CrossRefPubMed
2.
Rendu F, Brohard-Bohn B. The platelet release reaction: granules’ constituents, secretion and functions. Platelets. 2001;12(5):261–73.CrossRefPubMed
3.
Leytin V, Freedman J. Platelet apoptosis in stored platelet concentrates and other models. Transfus Sci. 2003;28(3):285–95.
4.
Reed GL. Platelet secretory mechanisms. In: Seminars in thrombosis and hemostasis. New York City: Thieme Medical Publishers; 2004. p. 441–450.
5.
Bertino AM, Qi XQ, Li J, Xia Y, Kuter DJ. Apoptotic markers are increased in platelets stored at 37 C. Transfusion. 2003;43(7):857–66.CrossRefPubMed
6.
Kile BT. The role of the intrinsic apoptosis pathway in platelet life and death. J Thromb Haemost. 2009;7(s1):214–7.CrossRefPubMed
7.
Zhao L, Zhang W, Chen M, Zhang J, Zhang M, Dai K. Aspirin Induces platelet apoptosis. Platelets. 2013;24(8):637–42.CrossRefPubMed
8.
Zharikov S, Shiva S. Platelet mitochondrial function: from regulation of thrombosis to biomarker of disease. Biochem Soc Trans. 2013;41(1):118–23.CrossRefPubMed
9.
Hait WN, Jin S, Yang JM. A matter of life or death (or both): understanding autophagy in cancer. Clin Cancer Res. 2006;12(7):1961–5.CrossRefPubMed
10.
Feng W, Chang C, Luo D, Su H, Yu S, Hua W, Chen Z, Hu H, Liu W. Dissection of autophagy in human platelets. Autophagy. 2014;10(4):76–85.CrossRef
11.
12.
Trikha M, Zhou Z, Timar J, Raso E, Kennel M, Emmell E, Nakada MT. Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res. 2002;62(10):2824–33.PubMed
13.
Sharma D, Brummel-Ziedins KE, Bouchard BA, Holmes CE. Platelets in tumor progression: a host factor that offers multiple potential targets in the treatment of cancer. J Cell Physiol. 2014;229(8):1005–15.CrossRefPubMed
14.
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(7):566–74.PubMed
15.
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(1):87.CrossRefPubMedPubMedCentral
16.
Wolmarans E, Mqoco TV, Stander A, Nkandeu SD, Sippel K, McKenna R, Joubert A. Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells. Cell Mol Biol Lett. 2014;19(1):98–115.CrossRefPubMed
17.
Stander A, Joubert F, Joubert A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs. Chem Biol Drug Des. 2011;77(3):173–81.CrossRefPubMed
18.
Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet–cancer loop. Eur J Intern Med. 2013;24(5):393–400.CrossRefPubMed
19.
Wallén NH, Ladjevardi M, Albert J, Bröijersén A. Influence of different anticoagulants on platelet aggregation in whole blood; a comparison between citrate, low molecular mass heparin and hirudin. Thromb Res. 1997;87(1):151–7.CrossRefPubMed
20.
Joubert A, Marais S. Influence of 2-methoxyestradiol on cell morphology and Cdc2 kinase activity in WHCO3 esophageal carcinoma cells. Biomed Res. 2007;28(1):9–16.CrossRefPubMed
21.
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(12):e52205.CrossRefPubMedPubMedCentral
22.
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(1):e53853.CrossRefPubMedPubMedCentral
23.
Seegers JC, de Kock M, Lottering ML, Grobler CJ, van Papendorp DH, Shou Y, Habbersett R, Lehnert BE. Effects of gamma-linolenic acid and arachidonic acid on cell cycle progression and apoptosis induction in normal and transformed cells. Prostaglandins Leukot Essent Fatty Acids. 1997;56(4):271–80.CrossRefPubMed
24.
Dickens C, Joffe M, Jacobson J, Venter F, Schüz 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;135(9):2173–82.CrossRefPubMedPubMedCentral
25.
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(14):2137–50.CrossRefPubMed
26.
Pretorius E. The role of platelet and fibrin ultrastructure in identifying disease patterns. Pathophysiol Haemost Thromb. 2007;36(5):251–8.CrossRef
27.
Goldstein J, Newbury DE, Joy DC, Lyman CE, Echlin P, Lifshin E, Sawyer L, Micheal JR. Scanning electron microscopy and X-ray microanalysis. 3rd ed. New York: Kluwer Academic/Plenum Publishers; 2002.
28.
Blatt NB, Glick GD. Signaling pathways and effector mechanisms pre-programmed cell death. Bioorg Med Chem. 2001;9(6):1371–84.CrossRefPubMed
29.
Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, Van Oers MH. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. 1994;84(5):1415–20.PubMed
30.
Bao Q, Shi Y. Apoptosome: a platform for the activation of initiator caspases. Cell Death Differ. 2007;14(1):56–65.CrossRefPubMed
31.
Funayama E, Chodon T, Oyama A, Sugihara T. Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: an important role in the pathogenesis of keloid. J Invest Dermatol. 2003;121(6):1326–31.CrossRefPubMed
32.
Periyasamy-Thandavan S, Jiang M, Schoenlein P, Dong Z. Autophagy: molecular machinery, regulation, and implications for renal pathophysiology. Am J Physiol Renal Physiol. 2009;297(2):244–56.CrossRef
33.
Gottlieb RA. Autophagy in health and disease. Salt Lake City: Academic Press; 2012.
34.
Pretorius E. Traditional coating techniques in scanning electron microscopy compared to uncoated charge compensator technology: looking at human blood fibrin networks with the ZEISS ULTRA Plus FEG-SEM. Microsc Res Tech. 2011;74(4):343–6.PubMed
35.
Schoenwaelder SM, Yuan Y, Josefsson EC, White MJ, Yao Y, Mason KD, O’Reilly LA, Henley KJ, Ono A, Hsiao S, Wilcox A, Roberts AW, Huang DC, Salem HH, Kile BT, Jackson SP. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood. 2009;114(3):663–6.CrossRefPubMed
36.
Gyulkhandanyan AV, Mutlu A, Freedman J, Leytin V. Markers of platelet apoptosis: methodology and applications. J Thromb Thrombolysis. 2012;33(4):397–411.CrossRefPubMed
37.
38.
Sabrkhany S, Griffioen AW, Oude Egbrink MGA. The role of blood platelets in tumor angiogenesis. Biochim Biophys Acta. 2011;1815(2):189–96.PubMed
39.
Mannello F, Medda V. Differential expression of MMP-2 and MMP-9 activity in megakaryocytes and platelets. Blood. 2011;118(24):6470–1.CrossRefPubMed
40.
Lloyd Matthew D, Pederick Richard L, Natesh R, Woo LWL, Purohit A, Reed MJ, Acharya KR, Potter BV. Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex with 667-coumate, a novel anti-cancer agent. Biochem J. 2005;385(3):715–20.CrossRefPubMedPubMedCentral
41.
Supuran CT, Scozzafava A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg Med Chem. 2007;15(13):4336–50.CrossRefPubMed
42.
Repsold L, Mqoco T, Wolmarans E, Nkandeu S, Theron J, Piorkowski T, Du Toit P, Van Papendorp D, Joubert AM. Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study. Biol Res. 2014;47(1):1–7.CrossRef
43.
Repsold L, Pretorius E, Joubert AM. 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 Int. 2014;14(1):48.CrossRefPubMedPubMedCentral
44.
Metadata
Title
Ex vivo apoptotic and autophagic influence of an estradiol analogue on platelets
Authors
Lisa Repsold
Etheresia Pretorius
Annie Margaretha Joubert
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2015
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-016-0048-z

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