title: Propolin C from propolis induces apoptosis through activating caspases, Bid and cytochrome c release in human melanoma cells.
abstract: We had demonstrated that two prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced apoptosis in human melanoma cells and significantly inhibited xanthine oxidase activity. Here, we have isolated a third compound called propolin C. The chemical structure of propolin C has been characterized by NMR and HRMS spectra, and was identical to nymphaeol-A. However, no biological activities of this compound have ever been reported. In the present study, propolin C effectively induced a cytotoxic effect on human melanoma cells, with an IC(50) of about 8.5 microM. DNA flow cytometric analysis indicated that propolin C actively induced apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of propolin C, we evaluated the effect of propolin C on induction of apoptosis-related proteins in human melanoma cells. The levels of procaspase-8, Bid, procaspase-3, and poly(ADP-ribose) polymerase were decreased in dose- or time course-dependent manners. Moreover, propolin C was capable of releasing cytochrome c from mitochondria to cytosol. The findings suggest that propolin C may activate a mitochondria-mediated apoptosis pathway. On other hand, propolin C is a potential antioxidant agent and shows a strong capability to scavenge free radicals and inhibit on xanthine oxidase activity with IC(50) of about 17.0microM. In conclusion, the isolation and characterization of propolin C from bee propolis are described for the first time, and this compound is a powerful inducer of apoptosis in human melanoma cells.
authors.affiliation: Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Section 1, Jen-Ai Road, 100, ROC, Taipei, Taiwan.
authors.forename: Chia-Nan
authors.initials: CN
authors.lastname: Chen
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Wu
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D002109:Caffeic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011429:Propolis / Q000737:chemistry*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002109:Caffeic Acids; D002352:Carrier Proteins; D005419:Flavonoids; D005609:Free Radicals; C480960:propolin C; D045304:Cytochromes c; D011429:Propolis; D014969:Xanthine Oxidase; D020169:Caspases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol