Bioactivity evaluation of natural product α-mangostin as a novel xanthone-based lysine-specific demethylase 1 inhibitor to against tumor metastasis

Abstract

Lysine-specific demethylase 1 (LSD1), which has been reported to be overexpressed in several human cancers, has recently emerged as an attractive therapeutic target for treating cancer. To date, almost all the developed LSD1 inhibitors are chemo-synthesized molecules, while α-mangostin is first characterized as xanthone-based natural inhibitor in the current study with IC₅₀ values of 2.81 ± 0.44 μM. Bioactivity study and docking analysis indicated that α-mangostin could inhibit MDA-MB-231 cells migration and evasion through inhibit intracellular LSD1 activity. These findings provides new molecular skeleton for LSD1 inhibitor study and should encourage further modification of α-mangostin to produce more potent LSD1 inhibitors with potential anticancer activity.

Keywords: Lysine-specific demethylase 1 inhibitor; Natural product; Tumor metastasis; Xanthone; α-mangostin.