Determination of Medicago orbicularis Antioxidant, Antihemolytic, and Anti-Cancerous Activities and Its Augmentation of Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells

The anti-lung cancer properties of the plant Medicago orbicularis have not been explored yet. Therefore, we identified its phytochemical composition and investigated the antioxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. The results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable hemolytic activities and modest antioxidant capacity. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells, with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts reduced the ratio of anti-apoptotic BCL-2/pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, the combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. We propose M. orbicularis as a potential source of anti-cancerous agents to manage the progression of lung cancer and its resistance to therapy.