Apoptolidin is a selective polyketide, apoptosis inducer produced by Nocardiopsis mainly inducing cell death in E1A-transformed cells and inhibiting the enzymatic activity of mitochondrial F0F1-ATPase. In addition, studies suggest that apoptolidin isomerizes in solution into isoapoptolidin (sc-202187) within the time frame of most cell-based assays, however isoapoptolidin's ability to inhibit mitochondrial F0F1--ATPase is over 10 fold less effective. Furthermore, studies show that apoptolidin induced apoptosis can be inhibited by BCL-2.
1. Salomon, A.R., et al. 2000. Proc. Natl. Acad. Sci. U.S.A. 97: 14766-14771. PMID: 11121076 2. Wender, P.A., et al. 2002. Org. Lett. 4: 3819-3822. PMID: 12599467 3. Wender, P.A., et al. 2006. Org. Lett. 8: 589-592. PMID: 16468718
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SalomonSalomon, et. al. (PubMed ID 11182320) established the following: Apoptolidin induces cell death independent of p53 status; BCL-2 inhibits apoptolidin action; Apoptolidin is dependent on the action of caspase-9; PARP is completely cleaved within 6 hours in mouse lymphoma cells in the presence of this polyketide. Salomon suggests based on these results that apoptolidin may target a mitochondrial protein. -SCBT Publication Review
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