Nanoemulsion-enhanced cytotoxicity of Cyperus scariosus essential oil in bladder and lung cancer cells: modulation of apoptosis, antioxidant, and cell cycle-related genes

Introduction The pharmacological application of essential oils in cancer therapy is frequently limited by poor bioavailability, physicochemical instability, and insufficient cytotoxic potency. Nano-enabled delivery systems have emerged as pharmacological strategies to enhance the therapeutic performance of natural products; however, their pharmacological mechanisms remain incompletely understood. Methods We investigated the pharmacological effects of a nanoemulsion incorporating Cyperus scariosus essential oil (NE-CSEO) in human bladder (5637) and lung (A549) cancer cells. Chemical composition was determined by GC-MS, while physicochemical properties were assessed by particle size, polydispersity index, and zeta potential. In vitro cytotoxic effects were evaluated by cell viability assays, and transcriptional responses were explored through gene expression analysis of apoptosis-, antioxidant-, and cell cycle-related genes. Results NE-CSEO formed a nanoscale emulsion (115 nm) and produced a concentration-dependent reduction in cell viability after 24 h of treatment, with measurable IC50 values of 4.99 ± 0.22 µg/mL and 2.73 ± 0.54 µg/mL in 5637 and A549 cells, respectively, whereas CSEO and NE-B did not reach 50% inhibition within the concentration ranges tested. At the transcriptional level, NE-CSEO increased BAX, CASP3, and CASP9 mRNA expression and decreased BCL2 mRNA expression in both cancer cell models. In bladder cancer cells, NE-CSEO additionally increased p21 mRNA expression and modulated CAT and SOD transcripts. Discussion These findings indicate that the enhanced in vitro growth-inhibitory activity of NE-CSEO is associated with transcriptional modulation of apoptosis-, antioxidant-, and cell cycle-related genes. However, direct functional confirmation of apoptosis, including protein-level apoptotic signaling and caspase activation, requires further investigation. NE-CSEO provides a basis for further preclinical investigation of nano-enabled natural compounds in cancer models.