Sökning: onr:"swepub:oai:DiVA.org:liu-27723" >
Mitochondria play a...
Mitochondria play a central role in apoptosis induced by a-tocopheryl succinate, an agent with antineoplastic activity : Comparison with receptor-mediated pro-apoptotic signaling
- Artikel/kapitelEngelska2003
Förlag, utgivningsår, omfång ...
-
2003-03-22
-
American Chemical Society (ACS),2003
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:liu-27723
-
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-27723URI
-
https://doi.org/10.1021/bi020527jDOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
a-Tocopheryl succinate (a-TOS) is a semisynthetic vitamin E analogue with high pro-apoptotic and anti-neoplastic activity [Weber, T et al. (2002) Clin. Cancer Res. 8, 863-869]. Previous studies suggested that it acts through destabilization of subcellular organelles, including mitochondria, but compelling evidence is missing. Cells treated with a-TOS showed altered mitochondrial structure, generation of free radicals, activation of the sphingomyelin cycle, relocalization of cytochrome c and Smac/Diablo, and activation of multiple caspases. A pan-caspase inhibitor suppressed caspase-3 and -6 activation and phosphatidyl serine externalization, but not decrease of mitochondrial membrane potential or generation of radicals. For a-TOS, but not Fas or TRAIL, apoptosis was suppressed by caspase-9 inhibition, while TRAIL- and Fas-resistant cells overexpressing cFLIP or CrmA were susceptible to a-TOS. The central role of mitochondria was confirmed by resistance of mtDNA-deficient cells to a-TOS, by regulation of a-TOS apoptosis by Bcl-2 family members, and by anti-apoptotic activity of mitochondrially targeted radical scavengers. Co-treatment with a-TOS and anti-Fas IgM showed their cooperative effect, probably by signaling via different, convergent pathways. These data provide an insight into the molecular mechanism, by which a-TOS kills malignant cells, and advocate its testing as a potential anticancer agent or adjuvant.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Dalen, HelgeÖstergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Patologi,Klinisk patologi och klinisk genetik
(författare)
-
Andera, L
(författare)
-
Nègre-Salvayre, A
(författare)
-
Augé, N
(författare)
-
Sticha, M
(författare)
-
Loret, A
(författare)
-
Terman, Alexei,1957-Linköpings universitet,Hälsouniversitetet,Patologi(Swepub:liu)alete63
(författare)
-
Witting, PK
(författare)
-
Higuchi, M
(författare)
-
Plasilova, M
(författare)
-
Zivny, J
(författare)
-
Gellert, N
(författare)
-
Weber, C
(författare)
-
Neuzil, Jiri,1958-Linköpings universitet,Hälsouniversitetet,Patologi(Swepub:liu)jirne62
(författare)
-
Linköpings universitetHälsouniversitetet
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Biochemistry: American Chemical Society (ACS)42:14, s. 4277-42910006-29601520-4995
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Weber, A
-
Dalen, Helge
-
Andera, L
-
Nègre-Salvayre, ...
-
Augé, N
-
Sticha, M
-
visa fler...
-
Loret, A
-
Terman, Alexei, ...
-
Witting, PK
-
Higuchi, M
-
Plasilova, M
-
Zivny, J
-
Gellert, N
-
Weber, C
-
Neuzil, Jiri, 19 ...
-
visa färre...
- Artiklar i publikationen
-
Biochemistry
- Av lärosätet
-
Linköpings universitet