AUTHOR=Lone Bashir Ahmad , Tabassum Misbah , Bhushan Anil , Rani Dixhya , Dhiman Urvashi , Ahmad Ajaz , Mir Hilal Ahmad , Gupta Prem N. , Mondhe D. M. , Gairola Sumeet , Gupta Prasoon 

TITLE=Trilliumosides K and L, two novel steroidal saponins from rhizomes of Trillium govanianum, as potent anti-cancer agents targeting apoptosis in the A-549 cancer cell line

JOURNAL=Frontiers in Chemistry

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1306271

DOI=10.3389/fchem.2023.1306271

ISSN=2296-2646

ABSTRACT=<p>Two novel steroidal saponins, trilliumosides K (<bold>1</bold>) and L (<bold>2</bold>), were isolated from the rhizomes of <italic>Trillium govanianum</italic> led by bioactivity-guided phytochemical investigation along with seven known compounds: govanoside D (<bold>3</bold>), protodioscin (<bold>4</bold>), borassoside E (<bold>5</bold>), 20-hydroxyecdysone (<bold>6</bold>), 5,20-hydroxyecdysone (<bold>7</bold>), govanic acid (<bold>8</bold>), and diosgenin (<bold>9</bold>). The structure of novel compounds 1-2 was established using analysis of spectroscopic data including 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-ESI-MS) data. All isolated compounds were evaluated for <italic>in vitro</italic> cytotoxic activity against a panel of human cancer cell lines. Compound <bold>1</bold> showed significant cytotoxic activity against the A-549 (Lung) and SW-620 (Colon) cancer cell lines with IC50 values of 1.83 and 1.85 µM, respectively whereas the IC50 value of Compound <bold>2</bold> against the A-549 cell line was found to be 1.79 µM. Among the previously known compounds <bold>3</bold>, <bold>5</bold>, and <bold>9</bold>, the cytotoxic IC50 values were found to be in the range of 5–10 µM. Comprehensive anti-cancer investigation revealed that Compound <bold>2</bold> inhibited <italic>in vitro</italic> migration and colony-forming capability in the A-549 cell line. Additionally, the mechanistic analysis of Compound <bold>2</bold> on the A-549 cell line indicated distinctive alterations in nuclear morphology, increased reactive oxygen species (ROS) production, and decreased levels of mitochondrial membrane potential (MMP). By upregulating the pro-apoptotic protein BAX and downregulating the anti-apoptotic protein BCL-2, the aforementioned actions eventually cause apoptosis, a crucial hallmark in cancer research, which activates Caspase-3. To the best of our knowledge, this study reports the first mechanistic anti-cancer evaluation of the compounds isolated from the rhizomes of <italic>T. govanianum</italic> with remarkable cytotoxic activity in the desired micromolar range.</p>