In silico and in vitro Characterizations of Rodent Tuber (Typhonium flagelliforme) Mutant Plant Isolates against FXR Receptor on MCF-7 Cells

Abstract

Typhonium flagelliforme (T. flagelliforme) is an Indonesian rodent tuber plant traditionally used to treat cancer diseases. Although gamma-ray irradiation has been used to increase the content in the chemical compounds of the T. flagelliforme plants with anticancer activity ten times effective, the specific effect of the isolated compounds from the mutant plants has never been reported yet. The potential cytotoxic agents were characterized via nuclear magnetic resonance spectroscopy, infrared spectroscopy, and mass spectrometry as stigmasterol and 7α-hydroxyl stigmasterol; and their anticancer activity was investigated. The in silico biochemical profile of the two compounds were analyzed by molecular docking and molecular dynamics simulation to confirm its interaction with the agonist binding site of Farsenoid X receptor (FXR). Stigmasterol and 7α-hydroxyl stigmasterol can act as a competitive regulator with a high-affinity for the FXR. The results also showed that stigmasterol and 7α-hydroxyl stigmasterol were the most potential and active fraction of the T. flagelliforme mutant plant against the MCF-7 human breast cancer cell line, with IC ₅₀ value 9.13 µM and 12.97 µM, compared with cisplastin as a control about 13.20 µM. These results demonstrate the potential of stigmasterol and 7α-hydroxyl stigmasterol in T. flagelliforme mutant plants to act towards cancer diseases.

graphical abstract