Salicin, an Extract from White Willow Bark, Inhibits Angiogenesis by Blocking the ROS-ERK Pathways

Abstract

Salicin has been studied as a potent antiinflammatory agent. Angiogenesis is an essential process for tumor progression, and negative regulation of angiogenesis provides a good strategy for antitumor therapy. However, the potential medicinal value of salicin on antitumorigenic and antiangiogenic effects remain unexplored. In this study, we examined the antitumorigenic and antiangiogenic activity of salicin and its underlying mechanism of action. Salicin suppressed the angiogenic activity of endothelial cells, such as migration, tube formation, and sprouting from an aorta. Moreover, salicin reduced reactive oxygen species production and activation of the extracellular signal-regulated kinase pathway. The expression of vascular endothelial growth factor was also decreased by salicin in endothelial cells. When the salicin was administered to mice, salicin inhibited tumor growth and angiogenesis in a mouse tumor model. Taken together, salicin targets the signaling pathways mediated by reactive oxygen species and extracellular signal-regulated kinase, providing new perspectives into a potent therapeutic agent for hypervascularized tumors.

Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells

“…In the present study, over-expression of TAS2R8 and TAS2R10 induced neuronal cell differentiation, and this was accompanied by ERK phosphorylation and the suppression of various CSC cell markers. These results are consistent with the observation that a bitter substance from willow bark, salicin, which is a TAS2R16 agonist was able to modulate neurite elongation in SH-SY5Y cells [43] and Kong and colleagues also identified an anti-cancer activity of salicin [44]. …”

Miyabeacin: A new cyclodimer presents a potential role for willow in cancer therapy

“…"Budburst" corresponded with the Weih definition of bud burst (stage 3) 33 and stage 10 as suggested by Saka and Kuzovkina 19 10 whereby "green tip elongates but leaves till remain in a tight cluster (>5 mm)". Tissue from multiple shoots was cut with scissors and immediately snap-frozen in liquid nitrogen at the following number of days after budburst (T): 3,4,5,6,7,8,9,10,12,15,30,45 and 60. For T3-T5 stages tissue from 2 plants (multiple stems) were pooled for each biological replicate.…”

“…However, recent work indicates that salicin itself may have anti-inflammatory properties via interaction with other components of the cytokine signalling complex 6 . Besides the established uses of aspirin for pain relief and also its prescription for the mitigation of thrombosis, via the involvement of COX-1 in thromboxane A2 mediated platelet aggregation 7 , there is now a renewed interest in the possibility of additional pharmacologies of salicinoids, for example in cancer therapy [8][9][10][11] . It has also been suggested that the medicinal activity of herbal extracts of willow cannot be accounted for by the levels of salicin alone 12,13 , indicating a potential for new bio-active or synergistic metabolites.…”

Anticancer prospection of salicin, a historical origin of aspirin

“…In a study, salicin was found to suppress the angiogenic activity on endothelial cells, such as migration, tube formation, and sprouting from an aorta. Additionally, it reduced reactive oxygen species (ROS) production and activation of the extracellular signal-regulated kinase pathway (Kong et al, 2014). …”