Linked Life Data

21527846

Source:http://linkedlifedata.com/resource/pubmed/id/21527846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-6-1
pubmed:abstractText
The natural isoquinoline alkaloid berberine exhibits a wide spectrum of biological activities including antitumor activity, but its mechanism of action remains to be fully elucidated. Here, we report that berberine induced apoptosis in human melanoma cells, through a process that involved mitochondria and caspase activation. Berberine-induced activation of a number of caspases, including caspases 3, 4, 7, 8, and 9. Pan-caspase inhibitor, z-VAD-fmk, and caspase-8 and caspase-9 inhibitors prevented apoptosis. Berberine also led to the generation of the p20 cleavage fragment of BAP31, involved in directing proapoptotic signals between the endoplasmic reticulum and the mitochondria. Treatment of SK-MEL-2 melanoma cells with berberine induced disruption of the mitochondrial transmembrane potential, release of cytochrome c and apoptosis-inducing factor from the mitochondria to the cytosol, generation of reactive oxygen species (ROS), and a decreased ATP/ADP ratio. Overexpression of bcl-xL by gene transfer prevented berberine-induced cell death, mitochondrial transmembrane potential loss, and cytochrome c and apoptosis-inducing factor release, but not ROS generation. N-acetyl-L-cysteine inhibited the production of ROS, but did not abrogate the berberine-induced apoptosis. Inhibition of extracellular signal-regulated kinase (ERK) phosphorylation, by using the mitogen-activated protein kinase/ERK kinase inhibitor PD98059, and reduction of B-RAF levels by silencing RNA induced cell death of SK-MEL-2 cells, and diminished the berberine concentration required to promote apoptosis. These data show that berberine-induced apoptosis in melanoma cells involves mitochondria and caspase activation, but ROS generation was not essential. Our results indicate that inhibition of B-RAF/ERK survival signaling facilitates the cell death response triggered by berberine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1473-5741
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
507-18
pubmed:dateRevised
2011-9-8
pubmed:meshHeading
pubmed-meshheading:21527846-Adenine Nucleotides, pubmed-meshheading:21527846-Antineoplastic Agents, Phytogenic, pubmed-meshheading:21527846-Apoptosis, pubmed-meshheading:21527846-Berberine, pubmed-meshheading:21527846-Blotting, Western, pubmed-meshheading:21527846-Caspases, pubmed-meshheading:21527846-Cell Cycle, pubmed-meshheading:21527846-Cell Line, Tumor, pubmed-meshheading:21527846-Chromatography, High Pressure Liquid, pubmed-meshheading:21527846-Cytochromes c, pubmed-meshheading:21527846-Down-Regulation, pubmed-meshheading:21527846-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:21527846-Flow Cytometry, pubmed-meshheading:21527846-G1 Phase, pubmed-meshheading:21527846-G2 Phase, pubmed-meshheading:21527846-Humans, pubmed-meshheading:21527846-Melanoma, pubmed-meshheading:21527846-Microscopy, Confocal, pubmed-meshheading:21527846-Mitochondria, pubmed-meshheading:21527846-Proto-Oncogene Proteins B-raf, pubmed-meshheading:21527846-RNA, Small Interfering, pubmed-meshheading:21527846-Reactive Oxygen Species, pubmed-meshheading:21527846-Signal Transduction
pubmed:year
2011
pubmed:articleTitle
Involvement of mitochondrial and B-RAF/ERK signaling pathways in berberine-induced apoptosis in human melanoma cells.
pubmed:affiliation
Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas - Universidad de Salamanca, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't