DMAPT‑D6 induces death‑receptor‑mediated apoptosis to inhibit glioblastoma cell oncogenesis via induction of DNA damage through accumulation of intracellular ROS

Glioblastoma (GBM) is an aggressive malignancy with a high rate of tumor recurrence after treatment conventional therapies. Parthenolide (PTL), sesquiterpene lactone extracted from the herb Tanacetum parthenium or feverfew, possesses anticancer properties against wide variety solid tumors. In present study, series PTL derivatives were synthesized and screened. An inhibitor, dimethylaminoparthenolide (DMAPT)‑D6, derivative prodrug DMAPT in which hydrogen dimethylamino group substituted for isotope deuterium, induced significant cytotoxicity GBM cells vitro cell cycle arrest at S‑phase dose‑dependent manner. Furthermore, mechanistic investigation indicated that through increasing levels intracellular accumulation reactive oxygen species (ROS), DMAPT‑D6 triggered DNA damage finally death receptor‑mediated extrinsic apoptosis cells, suggesting by initiated caspase‑dependent to remove damaged cells. Taken together, these data suggested ROS following results damage, thus, death‑receptor‑mediated apoptosis, highlighting potential as novel therapeutic agent GBM.