Lidocaine Induced Apoptosis in U937 Cells

Objectives: Local anesthetics are known for their ability to block voltage-dependent Na⁺ channels. However, it is also known that they have another effects on wound healing, thrombosis, and inflammatory responces of granulocytes and monocytes. In this study, we examined the effect of lidocaine on the growth of human monocytic U937 cells. Methods: The cells were cultured in the RPMI medium containing FBS and antibiotics in the presence or absence of lidocaine at various concentrations. Cell growth and death were monitored by WST assay, trypane blue exclusion assay, and flowcytometric analysis using PI staining. DNA ladder formation and collapse of the mitochondrial transmembrane potential(DYm) were monitored by agarose gel electrophoresis and by flowcytometric analysis using DiOC₆(3), respectively. Results: Lidocaine at concentrations above 3mM inhibited cell growth and induced cell death with DNA fragmentation and collapse of the DYm at concentrations above 12mM. The DNA fragmentation but not the reduction of DYm was inhibited by the broad spectrum inhibitor caspases, Z-VAD-fmk, followed by the reduction of cell death. The reduction of DYm was independent of caspase but the DNA fragmentation was a caspase-dependent process. In lidocaine-treated cells, nuclear chromatin condensation was observed, but apoptotic bodies with fragmented nuclei were not detected. Etoposide, an inhibitor of topoisomerase II, induced a typical apoptosis in U937 cells with DNA fragmentation and formation of apoptotic bodies, both of which were inhibitable by Z-VAD-fmk. Conclusions: These results indicate that lidocaine induced apoptosis in U937 cells by a mechanism different from that observed in etoposide-treated cells.