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

Abstract

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-α (HIF-1α) 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.

Natural products targeting the MAPK-signaling pathway in cancer: overview

“…Steroids are a wide class of chemical compounds in nature, all of which have a cyclopentano-perhydrophenanthrene parent nucleus in their structures. Certain steroidal saponins are already being used in cancer treatment studies (Bouabdallah et al 2023 ; Majnooni et al 2023 ). For example, timosaponin AIII is a steroid saponin that can play an anti-cancer role in different cancers, especially breast cancer.…”

Comparative Study of Biochemical Compounds and Its Related Therapeutic Efficacy of Iphiona Mucronata and Conyza Dioscorides

“…Presence of saponins play a vital role as antitumor agent by membrane disruption where, they can interact with cholesterol in cancer cell membranes, leading to pore formation and leakage of cell contents, ultimately causing cell death and increase immune stimulation by activating macrophages and natural killer cells, the body's natural defenses against cancer, to attack and destroy cancer cells (Isoldi et al, 2005). Furthermore, Angiogenesis inhibition: by preventing the formation of new blood vessels, which tumors need for growth and metastasis (Majnooni et al, 2023 andPodolak et al, 2023).…”

Plant-Based Oil-in-Water Food Emulsions: Exploring the Influence of Different Formulations on Their Physicochemical Properties

“…On the other hand, saponins are employed as foam stabilizers in beverages such as soft drinks and beers, and as food additives to enhance solubility [33]. They offer various health benefits, including anti-inflammatory, antibacterial, antiviral, anticancer, and cholesterol-lowering effects [34,35]. Saponin from Quillaja is derived from the bark of the Quillaja tree in Chile [5,36].…”