Sevoflurane anesthesia induces apoptosis and cell cycle arrest in NPC-039 nasopharyngeal cells
Purpose: To determine the effects of sevoflurane on NPC-039 nasopharyngeal carcinoma cells.
Methods: WST-8 assays and flow cytometry with annexin V/PI staining were used to analyze the effects of sevoflurane on growth and induction of apoptotic changes in NPC-039 cells. Cell viability was performed on a microplate reader.
Results: Treatment of NPC-039 cells with 4 – 10 μM sevoflurane significantly inhibited cell growth (p < 0.005) with a median inhibitory concentration of 6 μM. NPC-039 cells incubated with sevoflurane showed prominent nuclear fragmentation and chromatin condensation. NPC-039 cells that exhibited apoptotic symptoms increased from 23.34 to 56.77 % when duration of treatment was increased from 24 to 48 h. Sevoflurane-treated cells also expressed increased levels of Bax and cleaved caspase-3. Reactive oxygen species formation was also higher in sevoflurane-treated NPC-039 cells than in control. Pre-treatment with Z-VAD-FMK followed by incubation with sevoflurane partly reduced the population of apoptotic NPC-039 cells compared with cells treated with sevoflurane alone. The proportion of cells in S- and G0/G1 phases decreased and increased, respectively, when sevoflurane concentration was increased from 2 to 10 μM. Incubating NPC-039 cells with sevoflurane also markedly reduced levels of cyclin-dependent kinases including p15 INK4B, cyclin D1, p16 INK4A, and CDK-6. In contrast, pretreatment with ZVAD-FMK followed by incubation with sevoflurane increased p15 INK4B levels.
Conclusion: Sevoflurane inhibits nasopharyngeal carcinoma cell growth, activating apoptosis and inducing cell cycle arrest, thus suggesting its therapeutic potential for the treatment of nasopharyngeal carcinoma.
Keywords: Sevoflurane, Nasopharyngeal carcinoma, Chromatin, Condensation