Lung cancer remains one of the most lethal malignancies, often diagnosed at advanced stages, leading to limited treatment options. Thus, identifying natural products with potent anti-cancer activity is crucial for improving treatment outcomes. While the melittin from Apis mellifera (Mel-AM) has been extensively studied, the melittin from Apis florea (Mel-AF), a bee species native to Southeast Asia, remains relatively underexplored. These peptides were comparatively investigated against non-small cell lung cancer (NSCLC) cell lines, A549, NCI-H460, and NCI-H1975. Mel-AF demonstrated a superior cytotoxicity (cytotoxic concentration 50% (CC50) = 2.55–5.06 µg/mL) compared to Mel-AM (CC50 = 4.32–8.48 µg/mL). While both peptides induced apoptosis via the intrinsic mitochondrial pathway, Mel-AF exhibited a more pronounced effect, significantly enhancing apoptosis induction compared to Mel-AM. Both peptides inhibited cell migration and invasion; however, when combined with gefitinib, Mel-AF more effectively enhanced the drug’s inhibitory effects on the A549 and NCI-H460 cell lines compared to Mel-AM, underscoring its superior potential as a therapeutic agent. Altogether, we demonstrated that these peptides induced apoptosis in NSCLC cell lines, with Mel-AF having more pronounced effects, and the combination use of peptides with a chemotherapeutic drug showed synergistic effects against lung cancer cells, enhancing their practical use in lung cancer treatments.

Acute PM2.5 exposure has been implicated in lung cancer progression, yet its impact on genetically distinct NSCLC cells remains underexplored. This study investigates how mutation-specific transcriptional responses influence susceptibility to PM2.5-induced oncogenic alterations, focusing on A549 and NCI-H1975 cells. This provides preliminary insight into the transcriptomic effects of acute PM2.5 exposure in NSCLC cells with distinct oncogenic mutations (A549 and NCI-H1975), serving as a guide for understanding mutation-specific responses to environmental stress. Cells were exposed to PM2.5 (200 µg/mL, 24 h), followed by RNA sequencing and analysis. Gene ontology and pathway enrichment analyses were conducted to identify key molecular alterations associated with tumour progression. NCI-H1975 cells exhibited a stronger transcriptional response, with a higher fold change in differentially expressed genes (DEGs), indicating greater PM2.5 susceptibility. Upregulated genes were linked to oxidative stress, carcinogen activation, metabolic reprogramming, and therapy resistance, reinforcing tumour survival under PM2.5 stress. Conversely, the downregulation of tumour suppressor genes suggests immune suppression and potential immunotherapy resistance. This study reveals that acute PM2.5 exposure induces mutation-specific transcriptomic alterations in NSCLC, with EGFR-mutant cells exhibiting heightened oxidative stress, metabolic shifts, and immune evasion. The upregulation of key genes highlights the profound molecular impact of short-term exposure, paving the way for future studies on pollution-driven oncogenic mechanisms and resistance pathways.