Exposure of breast and lung cancer cells to a novel estrone analog prior to radiation enhances Bcl-2-mediated cell death

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dc.contributor.author Nolte, Elsie M.
dc.contributor.author Joubert, Annie M.
dc.contributor.author Lakier, Roy
dc.contributor.author Van Rensburg, Ado
dc.contributor.author Mercier, Anne Elisabeth
dc.date.accessioned 2018-12-14T05:44:00Z
dc.date.available 2018-12-14T05:44:00Z
dc.date.issued 2018
dc.description.abstract Following exposure of cells to gamma-radiation, a cascade of intracellular consequences may be observed in a semitemporal manner. This includes deoxyribonucleic acid (DNA) damage and reactive oxygen species (ROS) accumulation initially, with consequent signaling for DNA repair and facilitative regulation of the cell cycle. Failure to rectify the damage or ROS levels leads to induction of senescence or apoptosis. 2-Ethyl-3-O-sulfamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol), a 2-methoxyestradiole analog designed in silico for superior pharmacokinetics, was investigated for its potential to enhance apoptotic signaling and decrease the long-term survival of cells exposed to radiation. Sequential early intracellular effects within radiation-treated MCF-7 breastand A549 lung cancer cells pre-exposed to low-dose ESE-15-ol were investigated using various flow cytometric protocols, spectrophotometry, and microscopy. Long-term cellular survival and proliferation was examined using clonogenic studies, which demonstrated a significant decrease in the presensitized cells. Combination-treated cells exhibited increased superoxide formation, and decreased Bcl-2 expression and -phosphorylation. Induction of apoptosis and elevation of the sub-G1 phase was evident in the pre-exposed MCF-7 cells, although only minimally in the A549 cells at 48-h. These results indicate that low-dose ESE-15-ol may increase tumor response to radiation. Future studies will investigate the effect of ESE-15-ol pre-exposure on radiation-induced DNA damage and repair mechanisms. en_ZA
dc.description.department Physiology en_ZA
dc.description.department Radiology en_ZA
dc.description.librarian am2018 en_ZA
dc.description.sponsorship The National Research Foundation (NRF) (N00591, 89337), NRF Thuthuka (N00733, AOX981), NRF Incentive (N00375), Cancer Association of South Africa (CANSA) (AOW228), CANSA UP (AOV741), the Research Committee (School of Medicine) of the University of Pretoria (RESCOM) (AOR984), the Struwig-Germeshuysen Trust (AON074), the Research Development Program from the University of Pretoria (AOV840), and the Medical Research Council (AOW110). en_ZA
dc.description.uri www.mdpi.com/journal/ijms en_ZA
dc.identifier.citation Nolte, E.M., Joubert, A.M., Lakier, R. et al. 2018, 'Exposure of breast and lung cancer cells to a novel estrone analog prior to radiation enhances Bcl-2-mediated cell death', International Journal of Molecular Sciences, vol. 19, no. 10, art. 2887, pp. 1-22. en_ZA
dc.identifier.issn 1422-0067 (online)
dc.identifier.other 10.3390/ijms19102887
dc.identifier.uri http://hdl.handle.net/2263/68101
dc.language.iso en en_ZA
dc.publisher MDPI Publishing en_ZA
dc.rights © 2018 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). en_ZA
dc.subject Cancer en_ZA
dc.subject Radiation therapy en_ZA
dc.subject 2-Methoxyestradiol en_ZA
dc.subject ESE-15-ol en_ZA
dc.subject Radiosensitization en_ZA
dc.subject Apoptosis en_ZA
dc.subject Clonogenic studies en_ZA
dc.subject Mitogen-activated protein kinase (MAPK) en_ZA
dc.subject In vitro en_ZA
dc.subject Tumor cells en_ZA
dc.subject Paclitaxel en_ZA
dc.subject Estradiol en_ZA
dc.subject Combination en_ZA
dc.subject Deoxyribonucleic acid (DNA) en_ZA
dc.subject Reactive oxygen species (ROS) en_ZA
dc.subject B cell lymphoma 2 (Bcl-2) en_ZA
dc.title Exposure of breast and lung cancer cells to a novel estrone analog prior to radiation enhances Bcl-2-mediated cell death en_ZA
dc.type Article en_ZA


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