Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-2-27
pubmed:abstractText
HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1360-8185
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-33
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16502260-Animals, pubmed-meshheading:16502260-Apoptosis, pubmed-meshheading:16502260-Breast Neoplasms, pubmed-meshheading:16502260-Caco-2 Cells, pubmed-meshheading:16502260-Caspases, pubmed-meshheading:16502260-Cell Death, pubmed-meshheading:16502260-Cell Line, Tumor, pubmed-meshheading:16502260-Cell Survival, pubmed-meshheading:16502260-Female, pubmed-meshheading:16502260-HT29 Cells, pubmed-meshheading:16502260-Humans, pubmed-meshheading:16502260-Jurkat Cells, pubmed-meshheading:16502260-K562 Cells, pubmed-meshheading:16502260-Lactalbumin, pubmed-meshheading:16502260-Leukemia L1210, pubmed-meshheading:16502260-Lung Neoplasms, pubmed-meshheading:16502260-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16502260-Tumor Suppressor Protein p53, pubmed-meshheading:16502260-U937 Cells
pubmed:year
2006
pubmed:articleTitle
HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.
pubmed:affiliation
Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't