Natural Products: A Promising Therapeutics for Targeting Tumor Angiogenesis

Abstract

Tumor-associated angiogenesis is a key target for anti-cancer therapy. The imbalance between pro-angiogenic and anti-angiogenic signals elicited by tumor cells or tumor microenvironment always results in activating “angiogenic switch”. Tumor angiogenesis functions in multi-aspects of tumor biology, including endothelial cell apoptosis, tumor metastasis, and cancer stem cell proliferation. Numerous studies have indicated the important roles of inexpensive and less toxic natural products in targeting tumor angiogenesis-associated cytokines and apoptotic signaling pathways. Our current knowledge of tumor angiogenesis is based mainly on experiments performed on cells and animals, so we summarized the well-established models for angiogenesis both in vitro and in vivo. In this review, we classified and summarized the anti-angiogenic natural agents (Polyphenols, Polysaccharides, Alkaloids, Terpenoids, Saponins) in targeting various tumor types according to their chemical structures at present, and discussed the mechanistic principles of these natural products on regulating angiogenesis-associated cytokines and apoptotic signaling pathways. This review is to help understanding the recent progress of natural product research for drug development on anti-tumor angiogenesis.

Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology

“…Specifically, whatever natural products or chemical derivatives modulating angiogenesis share cardinal pathways that VEGF mediated, such as VEGFR2 pathway in vascular endothelial cells, HIF-1α/VEGF and its upstream transcriptional signaling in cancer cells, we concern and await the emergence of more potential targets for anti-angiogenesis therapy. Although other natural molecules in TCM also performed anti-angiogenesis property, comprising coumarins ( Wu et al, 2020 ), terpenoids ( Kamran et al, 2022 ), polysaccharides ( Li et al, 2021c ), and polyphenols ( Li et al, 2021c ; Marrero et al, 2022 ), they have no distinct difference in mechanisms in comparison with molecules we reported. Recently, angiopoietin (for instance, ang2) inhibition has been implied to be a strategy for overcoming the resistance of VEGF blockers in clinical, while the potential of natural molecules as angiopoietin inhibitors needs further observation ( Parmar and Apte, 2021 ).…”

Endometriosis-Associated Angiogenesis and Anti-angiogenic Therapy for Endometriosis

“…Smaller anti-angiogenic molecules, derived from natural products, have significant advantages over synthetic inhibitors. For instance, polyphenols, polysaccharides, alkaloids, terpenoids, and saponins containing natural products target tumor angiogenesis ( 133 ). Furthermore, smaller anti-angiogenic natural products can be more easily manufactured, confer lower cost, provide higher efficacy, and have little to no known toxicity ( 134 ).…”

Molecular and Immune Phenotypic Modifications during Metastatic Dissemination in Lung Carcinogenesis

“…VEGF is the main coordinator of new blood vessel formation from pre-existing endothelial cells on blood vessels [ 53 ]. Tumor cells and DTCs inside the hypoxic TME secrete high levels of pro-angiogenic factors such as basic fibroblast growth factor (bFGF), VEGF, PDGF-B, and TGF-β, which are key factors in juvenile vascular network formation in tumors [ 54 ]. Recently, the growth, metastasis, and angiogenesis of small cell lung cancer (SCLC) by profilin 2 (PFN2) was reported, which triggered vascular formation and angiogenesis via tumor-derived exosomes [ 55 ].…”