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: Chia-Nan Chen, Chia-Li Wu, Jen-Kun Lin
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 67 Issue 1 Pg. 53-66 (Jan 01 2004) ISSN: 0006-2952 [Print] England
• PMID: 14667928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BH3 Interacting Domain Death Agonist Protein
• BID protein, human
• Caffeic Acids
• Carrier Proteins
• Flavonoids
• Free Radicals
• propolin C
• Cytochromes c
• Propolis
• Xanthine Oxidase
• Caspases
• caffeic acid phenethyl ester
• Phenylethyl Alcohol

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• BH3 Interacting Domain Death Agonist Protein
• Caffeic Acids (pharmacology)
• Carrier Proteins (metabolism)
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cell Survival (drug effects)
• Cytochromes c (metabolism)
• DNA Fragmentation (drug effects)
• Enzyme Activation
• Flavonoids (pharmacology)
• Free Radicals (metabolism)
• Humans
• Melanoma (pathology)
• Mitochondria (drug effects, metabolism)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Propolis (chemistry)
• Xanthine Oxidase (antagonists & inhibitors)