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Induction of cancer...
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Neuzil, J.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
(author)
Induction of cancer cell apoptosis by a-tocopheryl succinate : Molecular pathways and structural requirements
- Article/chapterEnglish2001
Publisher, publication year, extent ...
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2001-02
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Wiley,2001
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-47470
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-47470URI
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https://doi.org/10.1096/fj.00-0251comDOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
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Colon cancer
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Programmed cell death
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Protein kinase C
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Vitamin E succinate
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Weber, T.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
(author)
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Schroder, A.Schröder, A., Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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Lu, M.Medical Center North, Vanderbilt University, Nashville, TN, United States
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Ostermann, G.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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Gellert, N.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
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Mayne, G.C.Flinders University of South Australia, Adelaide, SA, Australia
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Olejnicka, BeataLinköpings universitet,Hälsouniversitetet,Experimentell patologi(Swepub:liu)beaol03
(author)
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Negre-Salvayre, A.Nègre-Salvayre, A., Biochemistry Department, INSERM, Toulouse, France
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Sticha, M.Stícha, M., Faculty of Science, Charles University, Prague, Czech Republic
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Coffey, R.J.Medical Center North, Vanderbilt University, Nashville, TN, United States
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Weber, C.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
(author)
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Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany, Institute for Prevention of Cardiovascular Diseases, Pettenkoferstrasse 9, 80336 Munich, GermanyInstitute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
(creator_code:org_t)
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In:The FASEB Journal: Wiley15:2, s. 403-4150892-66381530-6860
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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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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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Linköping University