{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:51:55Z","timestamp":1760147515826,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]},{"name":"Cancer Association of South Africa","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]},{"name":"Research Committee (School of Medicine) of the University of Pretoria (RESCOM)","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]},{"name":"Struwig-Germeshuysen Trust","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]},{"name":"Research Development Program from the University of Pretoria","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]},{"name":"Medical Research Council","award":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"],"award-info":[{"award-number":["N00591","N00733","A0X981","N00375","A0W228","A0V741","A0R984","A0N074","AOV840","A0W110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24043592","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:28:46Z","timestamp":1676258926000},"page":"3592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Radiosensitization of Breast Cancer Cells with a 2-Methoxyestradiol Analogue Affects DNA Damage and Repair Signaling In Vitro"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-7416","authenticated-orcid":false,"given":"Elsie Magdalena","family":"Nolte","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Pretoria, Pretoria 0007, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-7554","authenticated-orcid":false,"given":"Anna Margaretha","family":"Joubert","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Pretoria, Pretoria 0007, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7902-7630","authenticated-orcid":false,"given":"Laurence","family":"Lafanech\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Pretoria, Pretoria 0007, South Africa"},{"name":"Team Cytoskeleton Dynamics and Nuclear Functions, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universit\u00e9 Grenoble Alpes, 38700 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-9879","authenticated-orcid":false,"given":"Anne Elisabeth","family":"Mercier","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Pretoria, Pretoria 0007, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrclinonc.2009.183","article-title":"Charged particles in radiation oncology","volume":"7","author":"Durante","year":"2010","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0360-3016(82)90392-3","article-title":"Tumor radioresistance in clinical radiotherapy","volume":"8","author":"Peters","year":"1982","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/0140-6736(91)90700-Y","article-title":"Prediction of cervical carcinoma response to radiotherapy","volume":"338","author":"West","year":"1991","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Maier, P., Hartmann, L., Wenz, F., and Herskind, C. (2016). Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010102"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.dnarep.2008.06.018","article-title":"Comparison of nonhomologous end joining and homologous recombination in human cells","volume":"7","author":"Mao","year":"2008","journal-title":"DNA Repair"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Helena, J.M., Joubert, A.M., Grobbelaar, S., Nolte, E.M., Nel, M., Pepper, M.S., Coetzee, M., and Mercier, A.E. (2018). Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041148"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1523\/JNEUROSCI.4213-15.2016","article-title":"DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis","volume":"37","author":"Dumitrache","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1093\/nar\/gkt304","article-title":"Clustered DNA damage induces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK","volume":"41","author":"Meyer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_9","first-page":"163","article-title":"The mechanisms of radiation-induced bystander effect","volume":"4","author":"Najafi","year":"2014","journal-title":"J. Biomed. Phys. Eng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1038\/sj.onc.1208439","article-title":"Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts","volume":"24","author":"Yang","year":"2005","journal-title":"Oncogene"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1080\/15476286.2015.1100795","article-title":"Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect","volume":"12","author":"Xu","year":"2015","journal-title":"RNA Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bbamem.2005.11.002","article-title":"Regulation of connexin expression","volume":"1719","author":"Oyamada","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/carcin\/19.1.1","article-title":"Functional role of estrogen metabolism in target cells: Review and perspectives","volume":"19","author":"Zhu","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sawicka, E., Saczko, J., Roik, J., Kulbacka, J., and Piwowar, A. (2020). Effect of Interaction between 17\u03b2-Estradiol, 2-Methoxyestradiol and 16\u03b1-Hydroxyestrone with Chromium (VI) on Ovary Cancer Line SKOV-3: Preliminary Study. Molecules, 25.","DOI":"10.3390\/molecules25215214"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cavalieri, E., and Rogan, E. (2021). The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158238"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6625","DOI":"10.1158\/1078-0432.CCR-05-0440","article-title":"A phase II multicenter, randomized, double-blind, safety trial assessing the pharmacokinetics, pharmacodynamics, and efficacy of oral 2-methoxyestradiol capsules in hormone-refractory prostate cancer","volume":"11","author":"Sweeney","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00280-010-1478-7","article-title":"A prospective phase II study of 2-methoxyestradiol administered in combination with bevacizumab in patients with metastatic carcinoid tumors","volume":"68","author":"Kulke","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ygyno.2009.05.042","article-title":"Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: A Hoosier Oncology Group trial","volume":"115","author":"Matei","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.drup.2003.10.001","article-title":"Mechanism of action of 2-methoxyestradiol: New developments","volume":"6","author":"Mooberry","year":"2003","journal-title":"Drug Resist. Update"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1158\/1078-0432.CCR-08-1599","article-title":"Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies","volume":"15","author":"Tevaarwerk","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1747-0285.2010.01064.x","article-title":"Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs","volume":"77","author":"Stander","year":"2011","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_22","first-page":"3267","article-title":"Confirming oral bioavailability of novel oestradiol analogues by liquid chromatography-tandem mass spectrometry in a murine model","volume":"29","author":"Mothibeli","year":"2018","journal-title":"Biomed. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00280-014-2653-z","article-title":"Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations","volume":"75","author":"Theron","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1475-2867-13-87","article-title":"Molecular crosstalk between apoptosis and autophagy induced by a novel 2-methoxyestradiol analogue in cervical adenocarcinoma cells","volume":"13","author":"Theron","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Visagie, M.H., Theron, A.E., Mqoco, T., Vieira, W.A., Prudent, R., Martinez, A., Lafanech\u00e8re, L., and Joubert, A.M. (2013). Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071935"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mercier, A.E., Prudent, R., Pepper, M.S., De Koning, L., Nolte, E., Peronne, L., Nel, M., Lafanech\u00e8re, L., and Joubert, A.M. (2021). Characterization of signalling pathways that link apoptosis and autophagy to cell death induced by estrone Analogues which reversibly depolymerize microtubules. Molecules, 26.","DOI":"10.3390\/molecules26030706"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12935-016-0367-5","article-title":"Autophagy induced by a sulphamoylated estrone analogue contributes to its cytotoxic effect on breast cancer cells","volume":"16","author":"Verwey","year":"2016","journal-title":"Cancer Cell Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00280-015-2903-8","article-title":"Antimitotic drugs in the treatment of cancer","volume":"76","author":"Visagie","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ijrobp.2004.03.005","article-title":"Role of cell cycle in mediating sensitivity to radiotherapy","volume":"59","author":"Pawlik","year":"2004","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/S0360-3016(01)01553-X","article-title":"Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiescent cells","volume":"50","author":"Masunaga","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1365-2184.2011.00789.x","article-title":"In vitro effects of an in silico-modelled 17\u03b2-estradiol derivative in combination with dichloroacetic acid on MCF-7 and MCF-12A cells","volume":"44","author":"Stander","year":"2011","journal-title":"Cell Prolif."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Helena, J., Joubert, A., Mabeta, P., Coetzee, M., Lakier, R., and Mercier, A. (2021). Intracellular Signaling Responses Induced by Radiation within an In Vitro Bone Metastasis Model after Pre-Treatment with an Estrone Analogue. Cells, 10.","DOI":"10.3390\/cells10082105"},{"key":"ref_33","first-page":"6394","article-title":"Induction of sister chromatid exchanges by extremely low doses of alpha-particles","volume":"52","author":"Nagasawa","year":"1992","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.18632\/oncotarget.12284","article-title":"Triple-negative breast cancer: Is there a treatment on the horizon?","volume":"8","author":"Yao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_35","first-page":"3691","article-title":"2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptors \u03b1 and \u03b2","volume":"62","author":"LaVallee","year":"2002","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.bcp.2015.02.011","article-title":"Dependency of 2-methoxyestradiol-induced mitochondrial apoptosis on mitotic spindle network impairment and prometaphase arrest in human Jurkat T cells","volume":"94","author":"Lee","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ydbio.2003.06.003","article-title":"Cell migration: Rho GTPases lead the way","volume":"265","author":"Raftopoulou","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0955-0674(02)00008-X","article-title":"Microtubules meet substrate adhesions to arrange cell polarity","volume":"15","author":"Small","year":"2003","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.2147\/DDDT.S152718","article-title":"Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines","volume":"12","author":"Nel","year":"2018","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1038\/sj.onc.1210605","article-title":"Orchestration of chromatin-based processes: Mind the TRRAP","volume":"26","author":"Murr","year":"2007","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e767","DOI":"10.1038\/cddis.2013.283","article-title":"Retinoblastoma protein regulates the crosstalk between autophagy and apoptosis, and favors glioblastoma resistance to etoposide","volume":"4","author":"Biasoli","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1172\/JCI28803","article-title":"The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer","volume":"117","author":"Bosco","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nolte, E., Joubert, A., Lakier, R., van Rensburg, A., and Mercier, A. (2018). Exposure of breast and lung cancer cells to a novel estrone analog prior to radiation enhances Bcl-2-mediated cell death. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102887"},{"key":"ref_44","first-page":"21","article-title":"Clonogenic cell survival assay","volume":"110","author":"Munshi","year":"2005","journal-title":"Methods Mol. Med."},{"key":"ref_45","first-page":"2573","article-title":"Clonogenic assay: Adherent cells","volume":"49","author":"Rafehi","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1084\/jem.103.5.653","article-title":"Action of x-rays on mammalian cells","volume":"103","author":"Puck","year":"1956","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2041-9414-4-1","article-title":"The shape of the radiation dose response for DNA double-strand break induction and repair","volume":"4","author":"Barnard","year":"2013","journal-title":"Genome Integr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fgene.2013.00131","article-title":"Micronuclei in genotoxicity assessment: From genetics to epigenetics and beyond","volume":"4","author":"Luzhna","year":"2013","journal-title":"Front. Genet."},{"key":"ref_49","first-page":"2217","article-title":"Impact of Apparent Antagonism of Estrogen Receptor \u03b2 by Fulvestrant on Anticancer Activity of 2-Methoxyestradiol","volume":"36","author":"Gorska","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1007\/s12035-015-9434-5","article-title":"Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line","volume":"53","author":"Gorska","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1158\/1078-0432.CCR-06-0678","article-title":"2-methoxyestradiol, an endogenous mammalian metabolite, radiosensitizes colon carcinoma cells through c-Jun NH2-terminal kinase activation","volume":"12","author":"Zou","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ijrobp.2010.10.080","article-title":"2-Methoxyestradiol, an endogenous estrogen metabolite, sensitizes radioresistant MCF-7\/FIR breast cancer cells through multiple mechanisms","volume":"80","author":"Salama","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hargrave, S.D., Joubert, A.M., Potter, B.V.L., Dohle, W., Marais, S., and Mercier, A.E. (2022). Cell Fate following Irradiation of MDA-MB-231 and MCF-7 Breast Cancer Cells Pre-Exposed to the Tetrahydroisoquinoline Sulfamate Microtubule Disruptor STX3451. Molecules, 27.","DOI":"10.3390\/molecules27123819"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/S0960-9822(00)00610-2","article-title":"A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage","volume":"10","author":"Paull","year":"2000","journal-title":"Curr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"31182","DOI":"10.1074\/jbc.M506591200","article-title":"Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase","volume":"280","author":"Dittmann","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1437","DOI":"10.1038\/cddis.2014.415","article-title":"PI3K\/Akt\/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways","volume":"5","author":"Chang","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10523","DOI":"10.1021\/bi00107a022","article-title":"Characterization of a major brain tubulin variant which cannot be tyrosinated","volume":"30","author":"Edde","year":"1991","journal-title":"Biochemistry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bbrc.2004.07.204","article-title":"Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiol","volume":"322","author":"Hagen","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","first-page":"396","article-title":"p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest","volume":"58","author":"Khan","year":"1998","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb1529","article-title":"Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest","volume":"9","author":"Mikule","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.4161\/cc.4.10.2061","article-title":"Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy","volume":"4","author":"Ikui","year":"2005","journal-title":"Cell Cycle"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:30:40Z","timestamp":1760121040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043592"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043592","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}