Steroid-Modulated Transcription Synergistically Forms DNA Double-Strand Breaks With Topoisomerase II Inhibitor.

ABSTRACT: The synergistic effects of drug combinations have emerged as a promising approach for achieving efficient cancer treatment. Through our exploration of drug combinations, we found that medroxyprogesterone acetate (MPA), a steroid, induced a synergistic antitumor effect in combination with the topoisomerase II inhibitor etoposide (ETP). In this study, we investigated the mechanisms underlying this synergistic effect for potential clinical applications. To elucidate the relevant mechanisms, we performed a cell viability assay, cell cycle analysis, DNA repair assays, detection of DNA double-strand breaks (DSBs) and the nuclear localization of topoisomerase II (Top2), and genome-wide detection of DSBs. MPA synergistically increased ETP-induced DSBs, resulting in cell cycle arrest in the G2/M ph

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12210024 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature