Apoptotic Potential and Antitumor Efficacy of Trilliumoside A: A New Steroidal Saponin Isolated from Rhizomes of Trillium govanianum

[Image: see text] Natural product-derived molecules exhibit potential as anticancer agents. Trilliumoside A, a new steroidal saponin, was obtained from rhizomes of Trillium govanianum, and its anticancer activity was investigated in the presented study. Trilliumoside A was investigated in a panel of cell lines, and it exhibited promising cytotoxic activity on the A549 cells (human lung cancer cells) with an IC(50) of 1.83 μM. The mechanism of cell death induced by Trilliumoside A in A549 cells and its anticancer potential in murine tumor models (EAC and EAT) were presented in the current research. Trilliumoside A was found to induce apoptosis in A549 cells by increasing the expression of various apoptotic proteins, such as Bax, Puma, cytochrome C, cleaved PARP, and cleaved caspase 3. Additionally, Trilliumoside A regulates the expression of p53, CDK2, and Cyclin A by decreasing the mitochondrial membrane potential, elevating reactive oxygen species, and stopping the growth of A549 cells in the synthesis phase (S) of the cell cycle. Trilliumoside A showed a considerable reduction in the tumor volume, the amount of ascitic fluid, and the total cell number without affecting the body weight of animals. Our results demonstrate that Trilliumoside A inhibits the proliferation of human lung cancer cells by inducing DNA damage, arresting the cell cycle, and activating the mitochondrial signaling pathway. The study demonstrated the potential of Trilliumoside A as a potential anticancer agent.