The research team, led by investigators at Iuliu Hațieganu University of Medicine and Pharmacy, tested eight widely used anaesthetic compounds—noradrenaline, lidocaine, rocuronium bromide, suxamethonium chloride, ropivacaine, fentanyl, ketamine and propofol—against a panel of five human cancer cell lines and one normal cell line. The tumour models included lung adenocarcinoma (A549), colorectal carcinoma (HCT116), hepatocellular carcinoma (HUH7), triple-negative breast cancer (MDA-MB-231) and cutaneous melanoma (SK-MEL-28), each genetically characterised for key mutations in p53, KRAS and BRAF. Normal human fibroblasts served as a healthy comparator.

The first and most striking result was the sheer heterogeneity of response. Using the MTT metabolic assay after 48 hours of exposure, the researchers calculated IC50 values—the concentrations needed to halve cell viability—that varied enormously between drugs and between cell lines. Lidocaine was highly potent against the colon and liver cancer cells, yet barely affected the triple-negative breast cancer line. Rocuronium bromide showed no inhibitory effect on liver and breast cancer cells but was strikingly active against melanoma. Fentanyl, at the doses and exposure times tested, failed to reduce metabolic activity in any of the cell lines. Ketamine and propofol, both intravenous agents, inhibited growth across most tumour models, with colon cancer cells proving the most sensitive to ketamine at 337 micromolar.

Importantly, the normal fibroblasts were generally more resistant than the tumour cells. Only four of the eight compounds—noradrenaline, ropivacaine, ketamine and propofol—reached an inhibitory threshold in the healthy cells, and for ropivacaine, ketamine and propofol the required doses were higher than those needed to suppress the cancer lines. That therapeutic window, the authors note, is a prerequisite for any future clinical relevance, since an ideal perioperative agent should harm tumour cells without damaging surrounding healthy tissue.

Beyond simple viability, the team probed whether the drugs could blunt two hallmarks of aggressive cancer: migration and the capacity to seed new colonies. In wound-healing assays, none of the compounds stimulated migration, and several strongly inhibited it, though in a strikingly cell-line-dependent fashion. Suxamethonium chloride nearly halted the movement of lung cancer cells, allowing only 23 percent wound closure, while lidocaine and ketamine were the most effective suppressors of breast cancer cell migration. Melanoma cells proved remarkably stubborn, with rocuronium bromide the only agent to completely block their movement. Colony formation assays told a similar story of selective vulnerability: propofol and ketamine inhibited colony formation in every tumour line tested, whereas noradrenaline was the sole compound able to suppress melanoma colonies.

Confocal fluorescence microscopy revealed the structural chaos the drugs inflict inside cells. Treated tumour cells displayed mitochondrial fragmentation and depolarisation, nuclear condensation, collapse of the F-actin cytoskeleton, cell swelling and the formation of tunnelling nanotubes—thin membrane bridges that emerge under cellular stress. The pattern of damage differed by drug and by tumour type. Lidocaine and noradrenaline wrecked the mitochondrial networks and actin filaments of lung cancer cells, while propofol triggered extensive mitochondrial fragmentation in liver cancer cells. Because cytoskeletal integrity and mitochondrial function underpin both motility and survival, these structural disruptions likely explain the functional losses measured in the migration and colony assays.

Flow cytometry added a dynamic dimension. Several compounds, most notably ketamine and propofol, pushed cells into a quiescent G0/G1 arrest, effectively freezing them before DNA replication. In lung cancer cells, ketamine trapped nearly 85 percent of the population in G0/G1, compared with 70 percent in untreated controls. In breast cancer cells, propofol froze 70 percent of cells in the same phase. Apoptosis measurements using PoPRO1 and 7-AAD staining showed that rocuronium bromide drove almost half of the triple-negative breast cancer population into late apoptosis within 24 hours, while colon cancer cells resisted all compounds, with no agent inducing more than 20 percent cell death. Melanoma cells were highly sensitive to noradrenaline and rocuronium, each triggering roughly 35 percent apoptosis.

At the molecular level, the picture grew more nuanced. Gene expression analysis of caspases 3, 8 and 9—the proteases that execute apoptosis—alongside the stress regulator NRF2, the inflammatory transcription factor NF-κB and the cyclin-dependent genes controlling cell cycle progression, revealed cell-specific signatures. In colon cancer cells, ropivacaine, fentanyl and ketamine significantly upregulated caspase 8, while rocuronium, suxamethonium and ropivacaine suppressed NRF2, hinting at a collapse of redox homeostasis. Liver cancer cells responded with a significant upregulation of CDK1-cyclin B and downregulation of CDK4-cyclin D, a pattern consistent with a compensatory attempt to escape a G1 blockade. Western blotting for cleaved PARP and cleaved caspase 3 confirmed that some drug–cell combinations, particularly lidocaine and ketamine in liver cancer cells, activate the classical caspase-dependent apoptosis pathway, whereas melanoma cells showed no detectable PARP or caspase 3 cleavage at all, suggesting they rely on entirely different death mechanisms.

The authors are careful to place these results in context. The experimental concentrations deliberately extended far beyond those achievable in patients, in order to characterise pharmacological activity and determine IC50 values. For propofol, lidocaine, ketamine, ropivacaine and fentanyl, clinically achievable perioperative plasma concentrations do fall within the tested ranges, but most experimental doses exceeded routine clinical exposure, and effects seen only at supraphysiological concentrations may not translate to the operating room. Succinylcholine, with a plasma half-life under one minute, poses particular interpretive challenges when compared against 48-hour in vitro exposures. The two-dimensional monolayer cultures also lack the stromal architecture, immune cells and extracellular matrix of real tumours, and perioperative neuroendocrine stress and transient immunosuppression cannot be recapitulated in a dish.

Nevertheless, the study’s central message is cautiously encouraging: across every assay, no anaesthetic compound stimulated tumour cell proliferation, and most acted as growth inhibitors. The pronounced heterogeneity—colon cancer cells resisting cell death while breast cancer cells succumbed to rocuronium, for instance—supports the authors’ vision of a personalised anaesthetic strategy, in which the drugs chosen for cancer surgery might one day be matched to the molecular profile of the tumour being removed. With randomised clinical trials to date showing largely neutral effects of anaesthetic technique on long-term oncological outcomes, the researchers argue that rigorous translational work, integrating pharmacokinetic data with clinically relevant exposure models and progressing through in vivo studies, is essential before laboratory observations can be turned into perioperative practice. For now, the operating room remains a place where the drugs that quiet the nervous system may also, quietly, influence the fate of lingering cancer cells.

Subject of Research: In vitro effects of commonly used anaesthetic compounds on the proliferation, migration, cell cycle and gene expression of solid tumour cell lines

Article Title: In Vitro Effects of Anaesthetic Compounds on a Panel of Solid Tumour Cell Lines—An Exploratory Study

Article References: Grajdieru, O., Sabo, A. C., Tigu, A. B., Ivancuta, A., Moldovan, C. S., Uhl, A., Ungurenasu, M. C., Balmez, A.-I., Moisescu, A., Pîrv, S., Nistor, M., Muresan, X.-M., Cenariu, D., Tomuleasa, C., & Constantinescu, C. (2026). In Vitro Effects of Anaesthetic Compounds on a Panel of Solid Tumour Cell Lines—An Exploratory Study. Journal of Cellular and Molecular Medicine, 30(18), Article e71307. https://doi.org/10.1111/jcmm.71307

Image Credits: AI Generated

DOI: 10.1111/jcmm.71307

Keywords: anaesthetic drugs, cancer cell lines, propofol, ketamine, lidocaine, tumour recurrence, perioperative medicine, apoptosis, cell cycle arrest, triple-negative breast cancer, in vitro study, cancer biology