Cytotoxic activity against human leukemia cells of Kaempferol-3-O-rhamnoside from Vietnamese Schima wallichii (DC.) Korth: A combination of in vitro and in silico insights

In the investigation of the cytotoxic activity against leukemia cells of Vietnamese medicinal plants, we identified the extract of Schima wallichii (DC.) Korth as capable of inhibiting several leukemia cell lines. In this study, we isolated a main compound as kaempferol-3-O-rhamnoside, marking the first report of this compound being isolated from the stem of Schima wallichii collected in Vietnam. In in vitro experiments, kaempferol-3-O-rhamnoside exhibited cytotoxic effects on three leukemia cell lines, HL-60 and KG-1. Regarding its mechanism of action, the compound effectively inhibited growth of HL-60 and KG-1 leukemia cell lines by activating caspase-3 and caspase-9 in both cell lines. Additionally, kaempferol-3-O-rhamnoside upregulated the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2 in these cell lines. In silico experiments revealed that docking simulations showed kaempferol-3-O-rhamnoside binds to both the allosteric site of procaspase-3 and the active site of PARP1, with binding energies of -7.36 and -10.76 kcal/mol, respectively. Kaempferol-3-O-rhamnoside demonstrated stable binding affinity with PARP1, characterized by significant hydrogen bonding, hydrophobic interactions, and pi-stacking in the molecular dynamic simulations. These results suggest that kaempferol-3-O-rhamnoside has the potential PARP1 inhibitor, making it a promising candidate for targeting leukemia cells. Moreover, it provides evidence for considering this compound in drug discovery and development targeting PARP1-related pathways.