Abstract
Our understanding of cell death used to consist in necrosis, an unregulated form, and apoptosis, regulated cell death. That understanding expanded to acknowledge that apoptosis happens through the intrinsic or extrinsic pathways. Actually, many other regulated cell death processes exist, including necroptosis, a regulated form of necrosis, and autophagy-dependent cell death. We also understand that apoptosis occurs beyond the intrinsic and extrinsic pathways with caspase independent forms of apoptosis existing. Our knowledge of the signaling continues to grow, and with that, so does our ability to target different parts of the pathways with small molecules. Marine natural products co-evolve with their targets, and these unique molecules have complex structures with exquisite biological activities and specificities. This article offers a review of our current understanding of the signaling pathways regulating cell death, and highlights marine natural products that can affect these signaling pathways.
Highlights
The golden mean, the yin and yang, homeostasis—no matter what we call it, nature tries to maintain a balance in its functions
Extrinsic apoptosis is described by the Nomenclature Committee on Cell Death (NCCD) as a regulated cell death process that is initiated by perturbations of the extracellular microenvironment that are detected by cell surface receptors, involve the activation of caspase 8, which can in some cases activate the intrinsic pathway, and is executed by caspase 3 [3]
Regulated cell death initiated by death receptor binding by their respective ligands—Fas ligand (FasL) for Fas and TNFα for tumor necrosis factor receptor 1 (TNFR1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for DR4 and DR5—leads to the formation of a death inducing signaling complex (DISC), which regulates the activation of caspase 8, and in some cases caspase 10 [3]
Summary
The golden mean, the yin and yang, homeostasis—no matter what we call it, nature tries to maintain a balance in its functions. We understand that apoptosis occurs beyond the intrinsic and extrinsic pathways with caspase-independent forms of apoptosis existing Reviewing all of these pathways in detail would be the object of a much longer article and has already been done recently in a succinct and entertaining play by Dr Douglas Green [2]. It is not surprising that many natural compounds are able to regulate apoptosis, and that there are myriad pathways by which they do so It would be impossible for a simple review to capture all marine natural products that can regulate apoptosis and there is no need to do so, as excellent recent reviews published in this journal and elsewhere have captured that. This article offers a review of our current understanding of the signaling pathways regulating cell death, and highlights selected marine natural products that can affect these signaling pathways
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