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Abstract

Chronic exposure to environmental carcinogens, mostly tobacco smoke, causes progressive genetic mutations and epigenetic changes in the bronchial epithelium, contributing to the multifactorial etiology of lung cancer. To treat this cancer subtype, new anti-cancer drugs still need to be discovered. The ethanolic extracts (70%) of fresh plant leaves consisting of mint, sidr, thyme, rosemary, basil, and neem were used compared with cisplatin as a positive control to treat A549 lung cancer cells. Cell viability, redox state, inflammation, hormonal signaling, and apoptotic pathway tests were used to assess biological activities. The extracts of neem and thyme showed more cytotoxicity at 200 µg/mL than cisplatin (10 µg/mL), lowering cell viability to 20.29% and 25.37%, respectively, whereas cisplatin reached 40.33%. Cisplatin and neem dramatically increased indicators including reactive oxygen species (ROS) (263.25%), nitric oxide (NO) (23.57 µM), and malondialdehyde (MDA) (8.14 nmol/mg) in conjunction with this anti-proliferative action, which was linked to an elevation of oxidative stress. Additionally, both therapies significantly reduced the cellular antioxidant defense, with thiol content falling to 40.36 % (neem) and 36.25% (cisplatin). At the same time, they inhibited important enzymatic activities, such as glutathione peroxidase (GPx) (44.39% vs. 35.2%), superoxide dismutase (SOD) (45.36% vs. 41.36%), and catalase (CAT) (43.04% vs. 36.12%). Neem extract and cisplatin treatments significantly increased tumor necrosis factor-alpha (TNF-α) (33.67 and 39.44 pg/mL) and interleukin-6 (IL-6) (38.51 and 34.21 pg/mL), which in turn caused apoptosis. Neem caused early (25.87%) and late (21.01%) apoptosis, which is similar to the 27.05% and 27.14% that cisplatin caused. Reduced BCL-2 and BCL-XL to as low as 37.22% and 41.22%, respectively, and increased caspase-9 and caspase-3 activity from a control baseline of approximately 0.85 to peaks of 3.25 and 3.89 U/mg protein. Additionally, both medicines demonstrated the strongest reductions in dihydrotestosterone (DHT) and prostate-specific antigen (PSA) levels, demonstrating their strong hormonal inhibitory and anti-proliferative properties. In contrast to basil and rosemary, which were less efficient, mint and sidr demonstrated considerable cytotoxicity (viability 45–55%). By lowering thiols to almost 55%, rosemary and thyme upset the redox equilibrium, whereas basil was the only one to lower CAT activity to 36.06%. All extracts reduced PSA/DHT levels and somewhat raised early apoptosis (10–15%), but their total bioactivity was still much less than that of the neem and cisplatin treatments. The current findings lend credence to leafy green plant's especially neem and thyme possible use in treating A549 lung cancer and serve as the foundation for further research.

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