Radiosensitization of breast cancer cells with a 2-methoxyestradiol analogue affects DNA damage and repair signaling in vitro
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Date
Authors
Nolte, Elsie Magdalena
Joubert, Anna Margaretha
Lafanechere, Laurence
Mercier, Anne Elisabeth
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Radiation resistance and radiation-related side effects warrant research into alternative
strategies in the application of this modality to cancer treatment. Designed in silico to improve the
pharmacokinetics and anti-cancer properties of 2-methoxyestradiol, 2-ethyl-3-O-sulfamoyl-estra-
1,3,5(10)16-tetraene (ESE-16) disrupts microtubule dynamics and induces apoptosis. Here, we investigated
whether pre-exposure of breast cancer cells to low-dose ESE-16 would affect radiation-induced
deoxyribonucleic acid (DNA) damage and the consequent repair pathways. MCF-7, MDA-MB-231,
and BT-20 cells were exposed to sub-lethal doses of ESE-16 for 24 h before 8 Gy radiation. Flow
cytometric quantification of Annexin V, clonogenic studies, micronuclei quantification, assessment of
histone H2AX phosphorylation and Ku70 expression were performed to assess cell viability, DNA
damage, and repair pathways, in both directly irradiated cells and cells treated with conditioned
medium. A small increase in apoptosis was observed as an early consequence, with significant
repercussions on long-term cell survival. Overall, a greater degree of DNA damage was detected.
Moreover, initiation of the DNA-damage repair response was delayed, with a subsequent sustained
elevation. Radiation-induced bystander effects induced similar pathways and were initiated via
intercellular signaling. These results justify further investigation of ESE-16 as a radiation-sensitizing
agent since pre-exposure appears to augment the response of tumor cells to radiation.
Description
Keywords
Cancer, Radiation, 2-methoxyestradiol analogue, ESE-16, Apoptosis, Radiosensitization, DNA damage and repair, Radiation-induced bystander effect, Microtubule dynamics, Actin, Deoxyribonucleic acid (DNA), SDG-03: Good health and well-being
Sustainable Development Goals
SDG-03:Good heatlh and well-being
Citation
Nolte, E.M.; Joubert, A.M.; Lafanechère, L.; Mercier, A.E. Radiosensitization of Breast Cancer Cells with a 2-Methoxyestradiol Analogue Affects DNA Damage and Repair Signaling In Vitro. International Journal of Molecular Sciences 2023, 24, 3592. https://doi.org/10.3390/ijms24043592.