Linked Life Data

16001965

Source:http://linkedlifedata.com/resource/pubmed/id/16001965

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-8-22
pubmed:abstractText
Vitamin E (VE) analogues, epitomized by alpha-tocopheryl succinate (alpha-TOS), are potent inducers of apoptosis and anti-cancer agents. Here, we tested their effect on the highly malignant N-type neuroblastoma (Nb) cells and their differentiated, neurone-like counterparts. Nb cells were highly susceptible to several VE analogues, while differentiated Nb cells were relatively resistant to alpha-TOS. The importance of caspase-9 rather than caspase-8, as judged by specific siRNAs studies, together with the loss of the inner mitochondrial potential, suggests that alpha-TOS triggers apoptosis in Nb cells via the mitochondrial pathway. Cultured Nb cells were sensitized to alpha-TOS by pre-treatment with Bcl-2, Bcl-xL or Mcl-1 siRNAs, while the malignant cell line was more resistant to the vitamin E analogue when Bax was knocked down. In contrast, overexpression of Bcl-2 in Nb cells rendered them more resistant to alpha-TOS-induced apoptosis. The resistance of differentiated Nb cells to alpha-TOS-mediated apoptosis occurred via two modes: first, by up-regulation of the anti-apoptotic Bcl-2 family proteins and second, by accumulation of decreased levels of reactive oxygen species when challenged with alpha-TOS. We conclude that alpha-TOS is highly selective in killing malignant brain cancer cells while relatively inert toward differentiated neuronal cells, and that vitamin E analogues may be novel therapeutics for the treatment of tumours such as neuroblastomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1448-56
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Alpha-tocopheryl succinate selectively induces apoptosis in neuroblastoma cells: potential therapy of malignancies of the nervous system?
pubmed:affiliation
Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Queensland, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't