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Induction of cancer...
Induction of cancer cell apoptosis by a-tocopheryl succinate : Molecular pathways and structural requirements
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- Neuzil, J. (author)
- 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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- Weber, T. (author)
- Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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- Schroder, A. (author)
- Schröder, A., Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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- Lu, M. (author)
- Medical Center North, Vanderbilt University, Nashville, TN, United States
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- Ostermann, G. (author)
- Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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- Gellert, N. (author)
- Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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- Mayne, G.C. (author)
- Flinders University of South Australia, Adelaide, SA, Australia
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- Olejnicka, Beata (author)
- Linköpings universitet,Hälsouniversitetet,Experimentell patologi
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- Negre-Salvayre, A. (author)
- Nègre-Salvayre, A., Biochemistry Department, INSERM, Toulouse, France
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- Sticha, M. (author)
- Stícha, M., Faculty of Science, Charles University, Prague, Czech Republic
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- Coffey, R.J. (author)
- Medical Center North, Vanderbilt University, Nashville, TN, United States
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- Weber, C. (author)
- 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
- English.
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 15:2, s. 403-415
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Keyword
- Colon cancer
- Programmed cell death
- Protein kinase C
- Vitamin E succinate
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Neuzil, J.
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Weber, T.
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Schroder, A.
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Lu, M.
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Ostermann, G.
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Gellert, N.
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show more...
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Mayne, G.C.
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Olejnicka, Beata
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Negre-Salvayre, ...
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Sticha, M.
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Coffey, R.J.
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Weber, C.
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- Articles in the publication
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The FASEB Journa ...
- By the university
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Linköping University