Verbascum ponticum (Stef.) Extract Induces Lung Cancer Apoptosis via Mitochondrial-Dependent Apoptosis Pathway

Non-small-cell lung carcinoma remains a significant health concern due to its high incidence and mortality rates. Traditional medicines play a central role in cancer therapy, with plant-derived bioactive compounds being studied for their potential to offer fewer side effects than conventional treatments. In traditional Kurdish medicine, different <i>Verbascum</i> species are used to treat burns, inflammation, and other conditions. While some species extracts have shown cytotoxic effects against several cancer cell lines like A549, the efficacy and mechanisms of action of the other species like <i>Verbascum ponticum</i> (<i>V. ponticum</i>) remain to be elucidated. Therefore, this study aimed to explore the effect of <i>V. ponticum</i> (Stef.) extract, collected from the Kurdistan region of the Iraq mountains, on A549 cells. A comprehensive approach was employed, utilizing immunocytochemical and functional analyses to assess apoptotic morphology, DNA fragmentation, alongside assays for cellular and mitochondrial function, proliferation, and viability. Additionally, the study investigated AIF mitochondrial translocation and evaluated mitochondrial membrane potential using the Rhodamine 123 assay. The results showed that the <i>V. ponticum</i> flower extract induced mitochondrial-mediated apoptosis in A549 cells via disruption of mitochondrial membrane potential, release of AIF, and translocation to the nucleus, independently of the caspase-3-activation pathway. These findings emphasize the potential of <i>V. ponticum</i> in lung cancer strategic treatments, meriting further phytochemical studies to identify the bioactive compounds it contains.