ALK and ERBB2 protein inhibition is involved in the prevention of lung cancer development by vincamine.

Abstract

According to the WHO report 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. Hence, in the present study, we explored the anticancer potential of vincamine by using network pharmacology, molecular docking, and in vitro approaches. Network pharmacology studies demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dose-dependent (0-500 μM) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 μΜ. The wound-healing assay showed that vincamine treatment (150 and 300 μM) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects.