Coompo Research Chemicals

The anti-cancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted anti-proliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through induction of G1 phase arrest and promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle- and differentiation-related genes, including up-regulation of p21cip and down-regulation of c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonoside-associated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML.

Previous studies have demonstrated that wogonoside has anti-inflammatory and anti-angiogenic activities. Wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells. In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris. The results showed that wogonoside promotes the expression of LC3-II and Beclin-1. Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which was associated with wogonoside-induced autophagy. Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.