Cephalothin, a First-Generation Cephem Antibiotic, Works as a Potent Inducer of Parthanatos

Parthanatos is a noncanonical form of regulated cell death mediated by the overactivation of poly(ADP-ribose) polymerase-1, yet its regulatory mechanisms are not fully understood. To fully elucidate its regulatory mechanisms, it is necessary to establish useful research tools to investigate parthanatos. We have previously identified the human fibrosarcoma HT1080 cells as highly sensitive cells to parthanatos, and cefotaxime, a 3rd-generation cephem antibiotic, as the parthanatos inducer. In this study, we comprehensively characterized the ability of various cephem antibiotics, including cephalothin (also called cefalotin) (CET), cefoxitin, ceftriaxone, cefoperazone, ceftezole, and cefalexin, to induce parthanatos. Among them, CET exhibited the lowest LD₅₀. Therefore, our results show that CET works as the more potent and useful parthanatos inducer.