Natural Products with Antiangiogenic and Antivasculogenic Mimicry Activity

Abstract

Angiogenesis is indispensible for tumor growth and metastasis. Antiangiogenic therapy is now a validated major strategy in cancer clinic; several small molecule angiogenic inhibitors have been successfully translated into clinic for multiple cancer indications. In the past decade, many natural products with potent antiangiogenic activity were explored and the underlying molecular mechanisms were revealed. One important mechanism is the inhibition of one or several steps in VEGF/VFGFR signaling pathway. Other factors (bFGF, HIF-1α, NF-κB etc.) capable of regulating angiogenesis, are also down-regulated by some natural products. Moreover, some of the antiangiogenic natural products also significantly inhibit vasculogenic mimicry (VM), another important vessel recruitment avenue in cancer, by regulating the key signaling of VM formation including VE-cadherin, EphA2, and Nodal signaling. In this mini-review, we summarized the natural products with suppressive effect on tumor angiogenesis and VM according to their diverse molecular mechanisms, and discussed the major direction of future research in this field.

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis

“…Epithelial to mesenchymal transition (ECM) related pathways and angiogenesis related pathways play an important role in this process (Shuai et al, 2020). Therefore, many signaling pathways are involved in the formation of vascular mimicry (Guan et al, 2016;Cai et al, 2020). Based on this understanding, we believe that Notch1 signaling is only one of the important targets in the process of VM in HCC cells.…”

Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling

“…Ten antiangiogenic drugs (seven small kinase inhibitors, two antibodies, and one fusion protein) are approved by Food and Drug Administration for multiple cancer indicators (Jayson, Kerbel, Ellis, & Harris, ). Currently, exploring antiangiogenic agent from natural products is emerging as an important research field, and many antiangiogenic natural products with diverse molecular structures have been discovered (Guan, Liu, Luan, et al, ; Guan, Luan, Lu, et al, ; Huang, Liang, Wang, et al, ; Huang, Wang, Liang, et al, ; Luan, Gao, Guan, et al, ; Wang, Chung, Zhang, et al, ).…”

The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation

“…Propolis composition is heterogeneous; however, this natural product and its main constituents have shown efficiency in the prevention of metastasis (Orsolic et al 2006). Different components from various propolis samples with antimetastatic activity have been identified such as isoflavonoids, caffeic acid phenethyl ester, artepillin C, nemorosone, galangin, cardanol (Peng et al 2012;Chien et al 2015;Guan et al 2016;Patel 2016). These constituents target various genetic and biochemical pathways involved in cancer progression, and the chemical composition of our propolis sample demonstrated the ability of inhibiting breast cancer cells metastasis.…”