TPOL triggers apoptosis with mitochondrial injury through activating a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signaling

• TPOL induces dose-dependent apoptosis in HEK293T cells via mitochondrial pathway, characterized by Bcl-2 downregulation, Bax and Cyto C upregulation, and caspase cascade activation. • TPOL triggers rapid ROS generation, mitochondrial membrane potential loss, and Cyto C release, all reversed by the ROS scavenger NAC, indicating ROS as a central mediator. • The p53 inhibitor pifithrin-α rescues TPOL-induced alterations in cell cycle regulators (p21, p27, Rb, CDK2) and apoptotic proteins, confirming p53-dependent signaling. • This study provides mechanistic insights into TPOL cytotoxicity, highlighting potential safety concerns for its use in photopolymerization applications and suggesting ROS/p53 axis as a therapeutic target.