Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwenese propolis

Cancer Lett. 2007 Jan 8;245(1-2):218-31. doi: 10.1016/j.canlet.2006.01.016. Epub 2006 Mar 3.

Abstract

We recently demonstrated that two new prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced cytotoxicity effect in human melanoma A2058 cells and shows a strong capability to scavenge free radicals. In this study, propolin A effectively induced a cytotoxic effect on five different cancer cell lines. Similar results were obtained for propolin B. DNA flow cytometric analysis and DNA fragmentation ladder indicated that propolin A and propolin B actively induced apoptosis in A2058 cells. To address the mechanism of the apoptosis effect of propolin A and propolin B, we evaluated the apoptosis-related proteins in A2058 cells. The levels of procaspase-8, Bid, procaspase-3, DFF45, and PARP were decreased in dose- and time course-dependent manners. Furthermore, also found propolin A and propolin B was capable of releasing cytochrome c from mitochondria to cytosol. The findings suggest that propolin A and propolin B may activate a mitochondria-mediated apoptosis pathway. On the other hand, our data show that propolin B inhibitied xanthine oxidase activity more efficiently than propolin A or CAPE. However, CAPE suppressed ROS-induced DNA strand breakage more efficiently than propolin A or propolin B. All these results indicated that propolin A and propolin B may trigger apoptosis of A2058 cells through mitochondria-dependent pathways and also shown that propolin A and propolin B were strong antioxidants.

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caffeic Acids / pharmacology
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • DNA Breaks
  • DNA Fragmentation / drug effects
  • DNA, Circular / drug effects
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Structure
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / pharmacology
  • Propolis / chemistry*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Xanthine Oxidase / metabolism

Substances

  • Caffeic Acids
  • DNA, Circular
  • Flavonoids
  • Reactive Oxygen Species
  • propolin A
  • propolin B
  • Cytochromes c
  • Propolis
  • Xanthine Oxidase
  • Caspase 3
  • Caspase 8
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol