RRR-alpha-tocopheryl succinate inhibits DNA synthesis and enhances the production and secretion of biologically active transforming growth factor-beta by avian retrovirus-transformed lymphoid cells

Nutr Cancer. 1995;24(2):171-85. doi: 10.1080/01635589509514405.

Abstract

The RRR-alpha-tocopheryl succinate form of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner in vitro. Analyses of conditioned medium (CM) from VES growth-inhibited cells revealed a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of TGF-beta-responsive Mv1Lu mink lung and murine CTLL-2 cell lines, 2) a combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, 3) neutralization of the antiproliferative activity by antibodies specific for TGF-beta, and 4) immunoprecipitation of metabolically labeled TGF-beta in CM from VES-treated C4-1 cells by use of TGF-beta-specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF-beta isoform-specific mRNAs; namely, VES does not alter the levels of the 3.9- and 4.1-kb TGF-beta 2 mRNAs, the 3.0-kb TGF-beta 3 mRNA, or the 2.5-, 2.7-, and 1.7-kb TGF-beta 4 mRNAs. The data show that VES inhibits C4-1 cell proliferation and induces the cells to produce and secrete active forms of TGF-beta, suggesting that one mechanism whereby VES inhibits C4-1 cell proliferation may be via the TGF-beta pathway for cellular growth control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Birds
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Bone Marrow Neoplasms / genetics
  • Bone Marrow Neoplasms / metabolism
  • Bone Marrow Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Transformed
  • Culture Media, Conditioned / pharmacology
  • DNA, Neoplasm / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Retroviridae
  • Tocopherols
  • Transcription, Genetic
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Antineoplastic Agents
  • Culture Media, Conditioned
  • DNA, Neoplasm
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Vitamin E
  • Tocopherols