Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

Abstract

Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

Marine Pharmaceuticals: A New Wave of Anti-angiogenic Drugs

“…Marine organisms including sponges, sponge-associated bacteria, gorgonia, molluscs, soft coral and actinomycetes, have been extensively explored for potential antiangiogenic agents. According to a recent review, currently more than 43 marine derived compounds are known to possess anti-angiogenic properties, out of which 10 have entered the different phases of clinical trials for cancer therapy [13]. These compounds show great structural and chemical diversity which includes saccharides, macrocycles, terpenes, peptides, saponins, pyrones, alkaloids and xanthones.…”

“…Although, its monotherapy has failed the clinical trials, it can still produce significant results in combination with chemotherapy. However, the toxicity and efficacy of the drug are questionable [13].…”

The Effect of Alcoholic Extract of Persian Gulf Chiton (lamyi) Shell on Angiogenesis in Chick Chorioallantoic Membrane

“…Angiogenesis not only plays an important role in physiological processes but is also involved in initiating and promoting several diseases such as cancer. As a hallmark of cancer, angiogenesis is considered as a powerful target to suppress tumor growth and metastasis [3]. The chick embryo chorioallantoic membrane (CAM) model is an extra embryonic membrane that is commonly used in vivo to study both angiogenesis and anti angiogenesis.…”

“…Biologically active molecules isolated from marine flora and fauna have applications in pharmaceuticals, nutritional supplements, cosmetics, agrochemicals, molecular probes, enzymes and fine chemicals [2]. Many marine derived natural products and their analogues have been reported to show antiangiogenic activities [3].…”

Search for Anti-angiogenic Substances from Natural Sources

“…Thus, selective anti-proliferative substances against endothelial cells are promising as angiogenic inhibitors with various modes of action, targeting not only VEGF but also other unknown molecules/pathways. 7,8) In the course of our study on bioactive substances from marine organisms, we focused on the search for novel anti-angiogenic substances by cell-based assay using human endothelial cells. In this paper, our studies concerning the search for selective anti-proliferative substances against human umbilical vein endothelial cells (HUVECs) from natural sources, together with mechanistic/synthetic studies of the active compounds, are reviewed.…”