Lung cancer is one of the deadliest cancers in the world. Introducing new promising agents can help the chemotherapeutic management of cancer. In the knowledge of oncology, plants are of special interest as a rich source of new antineoplastic and chemotherapeutic agents. Grandivittin (GRA) is one of the main constituents of Ferulago trifida Boiss. with established medicinal, phytochemical, and pharmacological properties. This study aimed to isolate and evaluate the antineoplastic potential of grandivittin and its underlying mechanisms in human lung cancer A549 cells. The viability of the A549 cells after being treated with 0.1, 0.4, 0.7, 1, and 1.3 mM of GRA for three following days was measured using the MTT method. The early apoptosis and late apoptosis were assessed by fluorescence-activated cell sorter analysis through annexin V/PI staining. The expression of apoptotic agents' genes (caspase 3, caspase 9, Bcl2, Bax, and P53) was evaluated by the RT-PCR method. GRA increased apoptotic cells and decreased cell viability in a dose- and time-dependent manner, in which only 50% of cells survived at a dose of 0.7 mM. The expression of Bax, P53, caspase 3, and caspase 9 genes in the A549 cells was significantly upregulated after GRA treatment compared to control cells (P < 0.05). On the other hand, Bcl2 was significantly downregulated after GRA treatment (P < 0.05). The results indicated that GRA can activate cell death in A549 lung carcinoma cells by inducing both DNA toxicity p53 and cascade-dependent pathways. Therefore, GRA may be a potential new therapeutic agent for the treatment of lung cancer.
Keywords: Apoptosis; Caspase; Ferulago trifida Boiss.; Grandivittin; Lung cancer; P53.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.