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Induction of cancer cell apoptosis by a-tocopheryl succinate : Molecular pathways and structural requirements

Neuzil, J. (författare)
Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany, Institute for Prevention of Cardiovascular Diseases, Pettenkoferstrasse 9, 80336 Munich, Germany
Weber, T. (författare)
Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
Schroder, A. (författare)
Schröder, A., Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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Lu, M. (författare)
Medical Center North, Vanderbilt University, Nashville, TN, United States
Ostermann, G. (författare)
Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
Gellert, N. (författare)
Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
Mayne, G.C. (författare)
Flinders University of South Australia, Adelaide, SA, Australia
Olejnicka, Beata (författare)
Linköpings universitet,Hälsouniversitetet,Experimentell patologi
Negre-Salvayre, A. (författare)
Nègre-Salvayre, A., Biochemistry Department, INSERM, Toulouse, France
Sticha, M. (författare)
Stícha, M., Faculty of Science, Charles University, Prague, Czech Republic
Coffey, R.J. (författare)
Medical Center North, Vanderbilt University, Nashville, TN, United States
Weber, C. (författare)
Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany, Institute for Prevention of Cardiovascular Diseases, Pettenkoferstrasse 9, 80336 Munich, Germany
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 (creator_code:org_t)
2001-02
2001
Engelska.
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 15:2, s. 403-415
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The vitamin E analog a-tocopheryl succinate (a-TOS) can induce apoptosis. We show that the proapoptotic activity of a-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented a-TOS-triggered apoptosis. More selective effectors indicated that a-TOS reduced PKCa isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCa inhibition in a-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCa overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of a-TOS-induced proapoptotic signals. Structural analogs revealed that a-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, a-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.

Nyckelord

Colon cancer
Programmed cell death
Protein kinase C
Vitamin E succinate
MEDICINE
MEDICIN

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