Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.
Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.
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