Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwenese propolis.
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.
Chen
Chia-Nan
CN
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Section 1, Jen-Ai Road, Taipei 100, Taiwan, ROC.
Wu
Chia-Li
CL
Lin
Jen-Kun
JK
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053960:DNA Breaks; D053938:DNA Fragmentation / Q000187:drug effects; D004270:DNA, Circular / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D011429:Propolis / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014969:Xanthine Oxidase / Q000378:metabolism
D002109:Caffeic Acids; D004270:DNA, Circular; D005419:Flavonoids; D017382:Reactive Oxygen Species; C477615:propolin A; C477616:propolin B; D045304:Cytochromes c; D011429:Propolis; D014969:Xanthine Oxidase; D053148:Caspase 3; D053181:Caspase 8; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol