Investigation of the effects of Sambucus nigra and bromelain on gasdermin-mediated pyroptosis and hsa-miR-30c-5p expression in A549 cells

Aims: Lung cancer is characterized by the highest global morbidity and mortality rates, thereby representing a considerable public health burden. At the molecular level, pyroptosis and apoptosis are of critical importance in tumorigenesis and in shaping the tumor microenvironment. Natural compounds have the capacity to influence mRNA and miRNA expression profiles, potentially regulating cancer-associated pathways. Sambucus nigra and bromelain are increasingly appreciated as important sources of bioactive natural compounds with potential health-promoting properties. In addition, the biological activities of these compounds have been investigated not only as single agents but also in combination with other bioactive molecules, revealing notably promising outcomes. In this context, the aim of this study was to investigate the effects of Sambucus nigra and bromelain on the expression of pyroptosis- and apoptosis-related genes in A549 cells. Additionally, the impact of the treatments on miRNA expression was examined to elucidate their potential regulatory roles.Methods: In this study, the dose-dependent effects of Sambucus nigra and bromelain on cell viability were assessed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The potential combined effects of the compounds were subsequently evaluated. Following administration, the expression profiles of pyroptosis- and apoptosis-related genes were analyzed by qRT-PCR (quantitative real-time PCR). The expression levels of hsa-miR-30c-5p were also examined by the same quantitative approach.Results: Sambucus nigra, bromelain, and their combination distinctly modulate genes involved in pyroptosis, apoptosis, and miRNA regulation, offering mechanistic insight into their potential anticancer mechanisms. Accordingly, GSDMD expression exhibited a significant increase following Sambucus nigra and combination treatments relative to the control, while a significant decrease was observed in bromelain-treated cells (p<0.05). Both single-compound and combination treatments resulted in a significant reduction in GSDME and Bcl-2 expression compared with the control (p<0.05). The expression of hsa-miR-30c-5p was significantly increased in single-compound treatment groups relative to the control, while a significant decrease was revealed in the combination treatment group (p<0.05).Conclusion: Collectively, these findings suggest that combinatorial treatment may offer a potential therapeutic approach for lung cancer via modulation of critical cell survival–related mechanisms. Additionally, further investigation incorporating advanced omics technologies is required to comprehensively elucidate the underlying molecular mechanisms.