Trilliumosides A-B, two novel steroidal saponins isolated from Rhizomes of Trillium govanianum as potent anticancer agents targeting apoptosis in A-549 cancer cell line.

Abstract

Two novel steroidal saponins, Trilliumosides A (1) and B (2) were isolated from the rhizomes of Trillium govanianum by 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 for in-vitro cytotoxic activity against a panel of human cancer cell lines. Compound 1 showed significant cytotoxic activity against A-549 (Lung) and SW-620 (Colon) cell lines with IC50 values of 1.83 and 1.85 {micro}M, whereas compound (2) IC50 value against A-549 cell line was found to be 1.79 {micro}M. Among previously known compounds (3), (5) and (9) their cytotoxic IC50 value was found to be in the range of 5-10 {micro}M. In detailed anticancer analysis compound (2) was seen inhibiting colony forming potential and in-vitro migration 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 of Trillium govanianumwith remarkable activity in the desired micro molar range. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/537170v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@14d9769org.highwire.dtl.DTLVardef@10f7658org.highwire.dtl.DTLVardef@22a38borg.highwire.dtl.DTLVardef@1f0b28_HPS_FORMAT_FIGEXP M_FIG C_FIG