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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-3-13
pubmed:abstractText
While certain cardiac glycoside compounds such as oleandrin, bufalin and digitoxin are known to be associated with potent cytotoxicity to human tumor cells, the mechanisms by which this effect is produced are not clear. We now demonstrate that incubation of human malignant melanoma BRO cells with oleandrin results in a time-dependent formation of reactive oxygen species (ROS). Use of Mito-SOX and dihydroethidine dyes revealed the presence of oleandrin-mediated superoxide anions. Formation of superoxide anions correlated with a loss in cellular viability, proliferation and cellular defense mechanisms such as GSH content. Oleandrin also resulted in an unusual time-dependent mitochondrial condensation in BRO cells that could be blocked with use of N-acetyl cysteine (NAC). NAC was also shown to block ROS formation and partially prevent oleandrin-mediated loss of cellular GSH. Taken as a whole, the data suggest that exposure of human tumor cells such as BRO to oleandrin results in the formation of superoxide anion radicals that mediate mitochondrial injury and loss of cellular GSH pools. These mechanisms play a role in cardiac glycoside mediated tumor cell injury. Conversely, incubation of NAC, a precursor to GSH, largely prevents oleandrin-mediated inhibition of proliferation and mitochondria structural changes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1359-4117
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-81
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Oleandrin-mediated oxidative stress in human melanoma cells.
pubmed:affiliation
Department of Experimental Therapeutics, Univ. Texas M. D. Anderson Cancer Center, Houston, TX 77054, USA. rnewman@mdanderson.org
pubmed:publicationType
Journal Article