RESUMO
BACKGROUND: 17ßH-neriifolin, a cardiac glycoside compound had been successfully isolated from Cerbera odollam leaves based on the bioassay guided-isolation procedure. The aim of these studies were to determine the in vitro anti-cancer and binding effects of 17ßH-neriifolin on Na+, K+-ATPase. METHODS: The in vitro anti-cancer effects were evaluated using Sulphorhodamine B and Hoescht 33342 assays. The Na+, K+-ATPase assay was carried out using Malachite Green assay. In silico molecular docking studies and in vitro malachite green assay were used to predict the binding activities of 17ßH-neriifolin on Na+, K+-ATPase and ouabain was also included as for comparison studies. RESULTS: The compound was tested against breast (MCF-7, T47D), colorectal (HT-29), ovarian (A2780, SKOV-3) and skin (A375) cancer cell lines that gave IC50 values ranged from 0.022 ± 0.0015 to 0.030 ± 0.0018 µM. The mechanism of cell death of 17ßH-neriifolin was further evaluated using Hoescht 33342 assay and it was found that the compound killed the cancer cells via apoptosis. 17ßHneriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were - 8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. CONCLUSION: The results had confirmed the anti-proliferative effects exerted by 17ßH-neriifolin in the breast, colorectal, ovarian and skin cancer cell lines. 17ßH-neriifolin had shown to cause apoptotic cell death in the respective cancer cell lines.17ßH-neriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were -8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. This is the first report to reveal that 17ßH-neriifolin managed to bind to the pocket of α-subunit of Na+.K+-ATPase.