Trilliumosides A-B, two novel steroidal saponins isolated from Rhizomes ofTrillium govanianumas potent anticancer agents targeting apoptosis in A-549 cancer cell line

Abstract

AbstractTwo novel steroidal saponins, Trilliumosides A (1) and B (2) were isolated from the rhizomes ofTrillium govanianumby bioactivity-guided phytochemical investigation along with seven known compounds protodioscin (3) govanoside B (4), borassoside E (5), 20-hydroxyecdysone (6), 5-20-hydroxyecdysone (7), govanic acid (8), and diosgenin (9). The structure of novel compounds 1-2 were established using spectroscopic methods such as 1D, 2D NMR data and HR-ESI-MS. The isolated compounds were evaluated forin-vitrocytotoxic activity against a panel of human cancer cell lines. Compound1showed significant cytotoxic activity against A-549 (Lung) and SW-620 (Colon) cell lines with IC50values of 1.83 and 1.85 µM, whereas compound (2) IC50value against A-549 cell line was found to be 1.79 µM. Among previously known compounds (3), (5) and (9) their cytotoxic IC50value was found to be in the range of 5-10 µM. In detailed anticancer analysis compound (2) was seen inhibiting colony forming potential andin-vitromigration in the A-549 cell line. Furthermore, the mechanistic study of compound (2) on the A-549 cell line revealed characteristic changes including nuclear morphology, increased ROS generation, and reduced levels of MMP. Above mentioned events eventually induce apoptosis, a key hallmark in cancer studies, by upregulating the pro-apoptotic protein BAX and downregulating the anti-apoptotic protein BCL-2 thereby activating Caspase-3. Our study reports the first mechanistic anticancer evaluation of the compounds isolated from the rhizomes ofTrillium govanianumwith remarkable activity in the desired micro molar range.Graphical abstract