Identification of a plant-derived terpenoid as a potential TET1 modulator in breast cancer

Background/Aim. Breast cancer progression is driven by dysregulated signaling pathways and epigenetic alterations. Plant-derived terpenoids have attracted significant attention as promising anticancer agents due to their ability to modulate key molecular and cellular targets. Ten-eleven translocation 1 (TET1) has been identified as an oncogenic factor in aggressive breast cancer subtypes, promoting tumor-supporting transcriptional activities at specific DNA sites and contributing to resistance against oxidative stress-mediated cell death. The aim of this study was to examine the potential of plant-derived terpenoids to target TET1 and to explore the correlation between TET1 modulation, oxidative stress, and apoptosis-mediated cell death in breast carcinoma. Methods. Molecular docking using a curvature-based docking approach and in vitro assessment of the effects of cryptotanshinone on cell viability, reactive oxygen species (ROS) generation, apoptosis, and the mRNA expression levels of TET1, SLC7A11, and GPX4 in MCF-7 cells were performed to investigate the anti-cancer potential of plant-derived terpenoids mediated by modulation of TET1 activity in breast cancer. Results. A high binding affinity of cryptotanshinone for the CXXC domain of TET1 was found, along with favorable drug-like properties, and cryptotanshinone was selected as the potent terpenoid for further analysis. In vitro evaluation revealed a dose-dependent reduction in cell viability of cryptotanshinone-treated MCF-7 cells and apoptotic induction. Additionally, gene expression analysis showed decrease in the mRNA levels of TET1, SLC7A11, and GPX4 in a dose-dependent manner, suggesting alterations in antioxidant defense pathway signaling. Conclusion. Cryptotanshinone may exert anticancer effects associated with apoptosis induction and oxidative stress modulation, potentially involving the epigenetic regulator TET1, in breast cancer cells. Further studies using animal models and clinical samples are necessary to confirm the therapeutic potential of cryptotanshinone in the treatment of breast can-cer.