Chemical Profiling, Molecular Docking, and Mechanistic Anticancer Activity of Pinus sylvestris Essential Oil in SH-SY5Y and U-87MG Cells

<i>Pinus sylvestris</i> essential oil (PSEO) has gained increasing interest as a natural anticancer candidate due to its bioactive phytochemical composition and potential to modulate apoptosis-related pathways. In this study, the chemical profile of PSEO was characterized by GC-MS, revealing oxygenated monoterpenes and monoterpene hydrocarbons as dominant constituents. Human brain (U-87MG) and peripheral nervous system (SH-SY5Y) tumor cells were treated with PSEO to evaluate cytotoxicity and mechanistic responses. Cell viability was assessed using the MTT assay, and 24-h IC₅₀ values were determined as 47.93 µg/100 µL for U-87MG and 71.63 µg/100 µL for SH-SY5Y, which were subsequently used for all mechanistic analyses. IC₅₀ exposure significantly increased intracellular ROS generation while reducing total antioxidant status, indicating oxidative stress-mediated cytotoxicity. Apoptosis-related ELISA assays demonstrated increased caspase-3 and caspase-9 activity, upregulated Bax, decreased Bcl-2, and a lowered Bcl-2/Bax ratio, collectively supporting the activation of the intrinsic mitochondrial apoptosis pathway. Molecular docking provided in silico evidence of favorable binding interactions between selected PSEO-associated ligands and apoptotic targets, consistent with experimentally observed biochemical outcomes. Overall, the findings suggest that PSEO exerts dose- and time-dependent anticancer effects and promotes mitochondrial apoptosis in U-87MG and SH-SY5Y cells, supporting its potential as a natural therapeutic candidate.