Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells

Lysine specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of the novel LSD1 inhibitor has great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed the antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR and C42B/MDVR cells with IC 50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 µM, respectively. It was a selective LSD1 inhibitor with an IC 50 value of 970.27 nM and concentration-dependently induced the significant accumulation of LSD1 substrates H3K9me1, H3K9me2 and H3K4me1 against DU145 cells. According to docking studies, it formed hydrogen bonds with Thr11, Lys14 and Arg8. Importantly, it displayed the potent antitumor efficacy in vivo and exhibited no obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B as a novel LSD1 inhibitor is a potential candidate to treat prostate cancer.