Olga Grajdieru, Alexandru Cristian Sabo, Adrian Bogdan Tigu, Andrei Ivancuta, Cristian Silviu Moldovan, Andrada Uhl, Miruna Cristina Ungurenasu, Andrada-Ioana Balmez, Ada Moisescu, Simina Pîrv, Madalina Nistor, Ximena-Maria Muresan, Diana Cenariu, Ciprian Tomuleasa, Catalin Constantinescu
Anaesthetic agents are essential for surgical procedures, yet their potential role on tumour cell biology remains incompletely understood. Emerging evidence suggests that these compounds can act both as protumor and antitumor agents, influencing cellular processes such as proliferation, migration and cell death mechanisms. Eight commonly used anaesthetic compounds were tested on five tumour cell lines-A549Luc2, HCT116Luc2, HUH7, MDAMB231Luc2 and SKMEL28Luc2. Cytotoxicity was assessed by MTT assay, while morphological changes were analysed using confocal fluorescence microscopy. Functional assays were used for wound healing, colony formation, flow cytometry for cell death and cell cycle and gene expression profiling was assessed by RT-qPCR. Morphological evaluation revealed profound compound-specific alterations, including mitochondrial fragmentation, nuclear condensation, osmotic swelling and cell structure alterations. Lidocaine and ropivacaine induced stress fibre formation and swelling, while tunnelling nanotubes were observed as signs of cellular stress. The structural changes are correlated with impaired migration, reduced colony formation and necrosis-dominated cell death. Gene expression analysis showed heterogeneous changes of apoptotic and cell cycle regulators, with caspase upregulation and NF-kB activation in specific cases. Anaesthetic agents exert pleiotropic, cell-line-dependent effects, primarily inhibiting tumour growth and motility in our cell models through structural destabilization and stress signalling. These findings underscore the need for advanced models to clarify clinical relevance and to confirm the best choice of anaesthesia technique tailored to the patient's specific cancer type.