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.