Study of the mechanism of action, molecular docking, and dynamics of anticancer terpenoids from Salvia lachnocalyx.

Among specialized metabolites, terpenoids are well-known for their cytotoxic activity. Several of them have been isolated from sage plants and assayed for their potential therapeutic use against cancer. In this study, we report the effects of three potent anticancer terpenoids previously isolated from Salvia lachnocalyx, including geranyl farnesol (1), sahandinone (2), and 4-dehydrosalvilimbinol (3) on cancer cell cycle alterations and reactive oxygen species (ROS) production. Interactions of compounds 1-3 with topoisomerase I were also investigated by using molecular docking and dynamics simulation. Accumulation of cells in sub-G1 phase of the cell cycle indicated that all tested compounds induce apoptosis in MOLT-4 cancer cells. Measurement of ROS production demonstrated that this mechanism is not involved in the induction of apoptosis. We suggest topoisomerase I inhibition as the mechanism of cytotoxic activity of compounds 1-3 based on docking and molecular dynamics (MD) calculations. These natural terpenoids could be considered as good candidates for further development as anticancer agents.