Chenopodium album metabolites act as dual topoisomerase inhibitors and induce apoptosis in the MCF7 cell line

Abstract

Desgalactotigonin (DGT) and oleanolic acid 3-O-β-D-glucuronide (OAG) were isolated from Chenopodium album seeds, characterized using spectral analysis and evaluated for cytotoxic activity against various cancer cell lines. DGT and OAG induced apoptosis in a human breast cancer cell line (MCF-7) and were found to effectively inhibit human topoisomerases I and II in vitro. The study of the mode of enzyme inhibition revealed that both acted as catalytic inhibitors. IC₅₀ values for DGT and OAG on MCF-7 cells were found to be 8.27 μM and 11.33 μM respectively. Using FACS and western blot analysis, the compounds were observed to block the cell cycle at S phase. Activation of caspases 7 and 9 suggested that caspase pathways were involved in inducing apoptosis.