Kemal Eker

BET inhibition enhances temozolomide sensitivity in cervical cancer cells through ALDH suppression and epigenetic reprogramming

Cervical cancer remains one of the most prevalent gynecological malignancies worldwide, and therapeutic resistance continues to limit the effectiveness of current treatment strategies. Aldehyde dehydrogenase 1 (ALDH1) has been associated with chemoresistance and cellular stress responses in cervical cancer, while bromodomain and extraterminal (BET) proteins have emerged as regulators of transcriptional and epigenetic programs involved in tumor progression. In this study, we investigated whether BET inhibition by JQ1 modulates cellular responses to temozolomide (TMZ) in cervical cancer cells. HeLa cells were treated with JQ1, TMZ, or TMZ + JQ1, alongside untreated controls. Cell viability and proliferation were evaluated using the WST-1 assay, and apoptotic cell death was assessed by Annexin V/propidium iodide staining and flow cytometry. Oxidative stress related changes were examined using malondialdehyde (MDA) measurements. Transcriptional alterations associated with epigenetic regulation were explored using the Human Epigenetic Chromatin Modification Enzymes RT² Profiler PCR Array and targeted RT-qPCR analysis of BET family members and ALDH isoforms. JQ1 and TMZ treatments reduced HeLa cell proliferation in a dose-dependent manner, with the combined treatment producing a modest additional antiproliferative effect compared with single agents. Flow cytometric analysis demonstrated increased apoptotic fractions in treated cells, particularly following combined exposure. MDA levels were reduced in JQ1-treated and JQ1 + TMZ treated cells, indicating altered oxidative stress status. Gene expression profiling revealed differential regulation of multiple chromatin-modifying enzymes involved in acetylation- and methylation-related pathways, while RT-qPCR analysis demonstrated coordinated transcriptional downregulation of BET family members and ALDH isoforms following combined treatment. This study demonstrates that BET inhibition by JQ1 influences cellular sensitivity to TMZ and is associated with altered oxidative stress parameters and transcriptional reprogramming of epigenetic regulators in cervical cancer cells. While further protein-level and functional validation is required to establish causal mechanisms, these findings support the potential of BET-targeted strategies to modulate therapeutic responses in cervical cancer.