Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-a (HIF-1a) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Automated summary

Saponins are high-molecular-weight natural compounds that consist of a non-polar moiety and a polar moiety containing sugars. They are found in various plants and marine organisms and have therapeutic effects, including anti-cancer properties. This study reviews the structural characteristics and anti-cancer effects of triterpenoid/steroid saponins, with a focus on their anti-angiogenic effects and related mechanisms. Saponins inhibit angiogenesis by targeting genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-a (HIF-1a), as well as inflammatory signaling pathways. The sugar moiety, monosaccharide units, and aglycone structure of saponins play important roles in their anti-angiogenic and anti-cancer activity. Extensive pre-clinical and clinical trial studies are recommended to further explore the potential of saponins for cancer treatment.