Combined Anastrozole and Antiplatelet Therapy Treatment Differentially Promotes Breast Cancer Cell Survival

Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study r...

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Vydáno v:Microscopy and microanalysis Ročník 26; číslo 3; s. 497 - 508
Hlavní autoři: Xulu, Kutlwano, Duarte, Raquel, Augustine, Tanya
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York, USA Cambridge University Press 01.06.2020
Oxford University Press
Témata:
Anastrozole
Anastrozole - pharmacology
Annexin A5
Apoptosis
Aspirin
Biological Applications
Biotechnology
Breast cancer
Breast Neoplasms - drug therapy
Cancer therapies
Cell death
Cell growth
Cell Line, Tumor
Cell survival
Cell Survival - drug effects
Clopidogrel
Combined treatment
Cytochrome
Cytotoxicity
Disorders
Enzymes
Flow cytometry
Humans
Iodides
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
MCF-7 Cells
Mortality
Necrosis
Penicillin
Phenotypes
Phosphatidylserine
Plasma
Platelet Aggregation Inhibitors - pharmacology
Propidium
Propidium iodide
Pseudopodia
Scanning electron microscopy
Statistical analysis
Survival
Therapeutic applications
Therapy
Thromboembolism
Thrombosis
Toxicity
Tumor cell lines
Tumors
South Africa
breast cancer
cell survival
antiplatelet therapy
anastrozole
ISSN:1431-9276, 1435-8115, 1435-8115
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Abstract Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.
AbstractList Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.
Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment strategy against cancer-associated thromboembolic disorders; however, the efficacy of such dual treatment has not been established. This study reports novel findings on the response of hormone-dependent breast cancer cell lines (MCF7/T47D) following 24 h treatment with Anastrozole, combined with Aspirin and Clopidogrel cocktail; and Atopaxar. Neutral red and lactate dehydrogenase assays were conducted to assess viability and cytotoxicity respectively. Flow cytometric Annexin-V/PI assay was used to assess the mode of cell death. Morphological alterations were studied using scanning electron microscopy. Statistical analysis was conducted using Statistica V13. Definitive outcomes were established with flow cytometric detection of phosphatidylserine exposure and propidium iodide staining, complemented with ultrastructural analysis. Results showed that a few cells were undergoing death mainly through secondary necrosis. Morphological features suggesting induced cell motility (pseudopodia/ruffled membranes) were observed in both cell lines; notably, T47D cells presented pronounced features than MCF7 cells. Overall, these findings suggest that such combined treatment may differentially promote cell survival, inducing a more aggressive breast cancer phenotype.
Author Augustine, Tanya
Xulu, Kutlwano
Duarte, Raquel
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  fullname: Xulu, Kutlwano
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  organization: 1School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193Johannesburg, South Africa
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  givenname: Raquel
  surname: Duarte
  fullname: Duarte, Raquel
  organization: 2Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193Johannesburg, South Africa
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  givenname: Tanya
  surname: Augustine
  fullname: Augustine, Tanya
  email: Tanya.Augustine@wits.ac.za
  organization: 1School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193Johannesburg, South Africa
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Snippet Thromboembolic disorders are the second leading cause of death in breast cancer. Antiplatelet therapy combined with cancer therapy is a potential treatment...
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SubjectTerms Anastrozole
Anastrozole - pharmacology
Annexin A5
Apoptosis
Aspirin
Biological Applications
Biotechnology
Breast cancer
Breast Neoplasms - drug therapy
Cancer therapies
Cell death
Cell growth
Cell Line, Tumor
Cell survival
Cell Survival - drug effects
Clopidogrel
Combined treatment
Cytochrome
Cytotoxicity
Disorders
Enzymes
Flow cytometry
Humans
Iodides
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
MCF-7 Cells
Mortality
Necrosis
Penicillin
Phenotypes
Phosphatidylserine
Plasma
Platelet Aggregation Inhibitors - pharmacology
Propidium
Propidium iodide
Pseudopodia
Scanning electron microscopy
Statistical analysis
Survival
Therapeutic applications
Therapy
Thromboembolism
Thrombosis
Toxicity
Tumor cell lines
Tumors
Title Combined Anastrozole and Antiplatelet Therapy Treatment Differentially Promotes Breast Cancer Cell Survival
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https://www.ncbi.nlm.nih.gov/pubmed/32241309
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