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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
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Weber, A (författare)
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- Dalen, Helge (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Patologi,Klinisk patologi och klinisk genetik
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Andera, L (författare)
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Nègre-Salvayre, A (författare)
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Augé, N (författare)
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Sticha, M (författare)
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Loret, A (författare)
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- Terman, Alexei, 1957- (författare)
- Linköpings universitet,Hälsouniversitetet,Patologi
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Witting, PK (författare)
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Higuchi, M (författare)
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Plasilova, M (författare)
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Zivny, J (författare)
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Gellert, N (författare)
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Weber, C (författare)
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- Neuzil, Jiri, 1958- (författare)
- Linköpings universitet,Hälsouniversitetet,Patologi
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(creator_code:org_t)
- 2003-03-22
- 2003
- Engelska.
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 42:14, s. 4277-4291
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Weber, A
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Dalen, Helge
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Andera, L
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Nègre-Salvayre, ...
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Augé, N
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Sticha, M
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visa fler...
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Loret, A
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Terman, Alexei, ...
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Witting, PK
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Higuchi, M
-
Plasilova, M
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Zivny, J
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Gellert, N
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Weber, C
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Neuzil, Jiri, 19 ...
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visa färre...
- Artiklar i publikationen
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Biochemistry
- Av lärosätet
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Linköpings universitet