@article{ajms20261112,
author={{S, Viacheslav and S., Jorge and C., Perez and J., Prajapati and A.J., Diaz and T., Wang},
title={Dual Epigenetic Impacts of Temozolomide on the Sensitivity of ER-positive and ER-negative Breast Cancer and Glioma Cells},
journal={American Journal of Medicine Studies},
volume={11},
number={1},
pages={8--15},
year={2026},
url={https://pubs.sciepub.com/ajms/11/1/2},
issn={2333-889X},
abstract={Temozolomide (TMZ) is an alkylating agent central to glioblastoma therapy. Its activity is classically attributed to DNA methylation. Still, the reactive methyl-diazonium ion it generates is an electrophile with the potential to modify multiple cellular nucleophiles, and growing evidence points to a protein-level dimension of TMZ's action¡ªincluding changes in histone methylation and in the activity of repair-associated enzymes. Because this protein-level activity appears cell-type-specific, treating resistance as a purely DNA-level event may overlook a mechanistic layer relevant to why tumor types differ in their sensitivity to the drug. In this course-based undergraduate research experience (CURE) in Clinical Chemistry, we evaluated the cytotoxic response of three cancer cell lines ¡ª MCF-7 (estrogen receptor-positive breast cancer), MDA-MB-231 (triple-negative breast cancer), and U87 (glioblastoma) to TMZ. Cells were treated for 48 hours across a 50¨C200 ¦ÌM concentration range, and the MTS assay quantified viability. The Wilcoxon signed-rank test was used to assess significance relative to untreated controls, and four-parameter logistic (4PL) regression was used to model dose-response and estimate IC?? values. Both breast cancer lines were sensitive to TMZ, with IC?? values of 59.0 ¦ÌM (MCF-7) and 46.4 ¦ÌM (MDA-MB-231), whereas U87 glioblastoma cells were markedly less responsive (nominal IC?? 213.7 ¦ÌM). Because only half of the U87 dataset reached statistical significance, its IC?? is considered preliminary. The greater resistance of glioblastoma is consistent with MGMT-mediated repair of O6-methylguanine, but is best interpreted alongside a protein-level dimension of TMZ's action observed in our prior work: in glioma cells, increasing TMZ concentrations were associated with a decrease in histone methylation and a concentration-dependent, bimodal change in the activity of the histone demethylase LSD1 (KDM1A) ¡ª largely preserved at 100 ¦ÌM or below and reduced at higher concentrations ¡ª an enzyme itself linked to DNA repair. Considered together, these DNA- and protein-level effects offer a fuller account of TMZ sensitivity than DNA damage alone. Beyond these biological findings, the project gave undergraduates hands-on training in experimental design, statistical analysis, and scientific communication, illustrating the value of embedding authentic research within the undergraduate curriculum.},
doi={10.12691/ajms-11-1-2}
publisher={Science and Education Publishing}
}