Oxidative Stress-Associated Apoptotic Responses Induced by Lantana camara L. Flower–Derived Zinc Oxide Nanoparticles in Human Non-Small Cell Lung Cancer (NCI-H460) Cells

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for safer and more effective therapeutic strategies. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized via a green, biogenic approach using Lantana camara L. flower aqueous extract and evaluated for their anticancer potential against human non-small cell lung cancer (NSCLC) NCI-H460 cells. The biosynthesized ZnO NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and particle size analysis, confirming the formation of nanocrystalline ZnO. LC-MS profiling of the Lantana camara flower extract revealed the presence of several bioactive phytochemicals, including phenolic compounds, terpenoids, fatty acids, and alkaloids, which may contribute to the reduction and stabilization of ZnO NPs during green synthesis. Cytotoxicity assessment of ZnO NPs using MTT and trypan blue exclusion assays revealed a dose-dependent reduction in cell viability, with an IC50 value of 50 µg/mL. Mechanistic investigations demonstrated that ZnO NP exposure induced significant oxidative stress, evidenced by increased nitric oxide, lipid peroxidation, and reactive oxygen species levels, along with depletion of intracellular glutathione. Apoptotic cell death was further confirmed by nuclear DNA fragmentation, mitochondrial membrane depolarization, and G0/G1 phase cell cycle arrest. Quantitative real-time PCR analysis revealed upregulation of the pro-apoptotic genes Bax and p53, accompanied by downregulation of the anti-apoptotic gene Bcl-2, indicating activation of a mitochondrial-dependent intrinsic apoptotic pathway. Collectively, these findings suggest that Lantana camara L. flower-mediated ZnO nanoparticles induced apoptotic responses associated with oxidative stress in NSCLC cells, highlighting their ability as an eco-friendly nanoplatform for further anticancer investigations.