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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 ...

  • 2001-02
  • Wiley,2001
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-47470
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-47470URI
  • https://doi.org/10.1096/fj.00-0251comDOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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

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

Added entries (persons, corporate bodies, meetings, titles ...)

  • Weber, T.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany (author)
  • Schroder, A.Schröder, A., Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany (author)
  • Lu, M.Medical Center North, Vanderbilt University, Nashville, TN, United States (author)
  • Ostermann, G.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany (author)
  • Gellert, N.Institute for Prevention of Cardiovascular Diseases and Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany (author)
  • Mayne, G.C.Flinders University of South Australia, Adelaide, SA, Australia (author)
  • Olejnicka, BeataLinköpings universitet,Hälsouniversitetet,Experimentell patologi(Swepub:liu)beaol03 (author)
  • Negre-Salvayre, A.Nègre-Salvayre, A., Biochemistry Department, INSERM, Toulouse, France (author)
  • Sticha, M.Stícha, M., Faculty of Science, Charles University, Prague, Czech Republic (author)
  • Coffey, R.J.Medical Center North, Vanderbilt University, Nashville, TN, United States (author)
  • 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)
  • 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)

Related titles

  • In:The FASEB Journal: Wiley15:2, s. 403-4150892-66381530-6860

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