Apoptolidin: induction of apoptosis by a natural product.
Apoptolidin is a natural product that selectively induces apoptosis in several cancer cell lines. Apoptosis, programmed cell death, is a biological key pathway for regulating homeostasis and morphogenesis. Apoptotic misregulations are connected with several diseases, in particular cancer. The extrinsic way to apoptosis leads through death ligands and death receptors to the activiation of the caspase cascade, which results in proteolytic degradation of the cell architecture. The intrinsic pathway transmits signals of internal cellular damage to the mitochondrion, which loses its structural integrity, and forms an apoptosome that initiates the caspase cascade. Compounds which regulate apoptosis are of high medical significance. Many natural products regulate apoptotic pathways, and apoptolidin is one of them. The known synthetic routes to apoptolidin are described and compared in this Review. Selected further natural products which regulate apoptosis are introduced briefly.
Daniel
Peter T
PT
Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charité, Humboldt University of Berlin, Germany.
Koert
Ulrich
U
Schuppan
Julia
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001688:Biological Products; D020169:Caspases / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D001688:Biological Products; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D018942:Macrolides; D064429:Fatty Acid Synthases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; C114125:apoptolidin