A Pt(II) complex bearing N-heterocycle ring induced ferroptotic cell death in ovarian cancer

J Inorg Biochem. 2024 Feb 6;253:112502. doi: 10.1016/j.jinorgbio.2024.112502. Online ahead of print.ABSTRACTCisplatin is a widely used chemotherapeutic agent which interacts with DNA to form Pt-DNA adducts, leading to DNA double-strand breaks and apoptosis. Resistance is the major obstacle in the clinical application of cisplatin. A quinoline derivative based Pt(II) complex PtQ was synthesized and characterized. As an analogue of cisplatin, PtQ demonstrated a novel anticancer mechanism in ovarian cancer. PtQ caused excessive production of reactive oxygen species (ROS), which triggered ferroptotic cell death in ovarian cancer. Cystine/glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4) which alleviate lipid peroxidation were both downregulated in PtQ-treated SKOV3 cells. Furthermore, PtQ induced DNA single-strand breaks and suppressed the expression of single-strand breaks repair protein PARP1. Mechanism studies demonstrated that PtQ can hopefully bypass the signaling pathways mediated cisplatin resistance in ovarian cancer.PMID:38335582 | DOI:10.1016/j.jinorgbio.2024.112502
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Source Type: research