title: Dykellic acid inhibits drug-induced caspase-3-like protease activation.
abstract: Dykellic acid is a novel microbial metabolite isolated from the broth of Westerdykella multispora F50733. Investigations on the molecular function of dykellic acid revealed that this compound partially inhibits calcium influx, resulting in a decrease in Ca(2+)-dependent endonuclease activation and DNA fragmentation induced by camptothecin. In our experiments, active caspase-3-like protease cleavage of procaspase-3, PARP, and cytosolic cytochrome c was inhibited by dykellic acid in a concentration-dependent manner when the apoptosis was induced by camptothecin as well as doxorubicin. We confirmed that dykellic acid did not bind to camptothecin using surface plasmon resonance analysis. These results suggest that dykellic acid inhibits drug-induced apoptosis via a caspase-3-like protease-suppressing mechanism. Our data provide important information on the mechanism of action of dykellic acid and indicate that this compound may be employed in the treatment of specific caspase-3-like protease-mediated diseases.
authors.affiliation: Korea Research Institute of Bioscience & Biotechnology, Taejon 305-333, Republic of Korea. sang@mail.kribb.re.kr
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Youk
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yung-Hee
authors.initials: YH
authors.lastname: Kho
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Sung-Uk
authors.initials: SU
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002166:Camptothecin / Q000378:metabolism / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004720:Endonucleases / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D013997:Time Factors; D020298:U937 Cells
chemical_list: D003574:Cytochrome c Group; D004792:Enzyme Precursors; D011422:Propionates; D011753:Pyrones; C406051:dykellic acid; D011065:Poly(ADP-ribose) Polymerases; D004720:Endonucleases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002118:Calcium; D002166:Camptothecin