RRR‐α‐tocopheryl succinate inhibits DNA synthesis and enhances the production and secretion of biologically active transforming growth factor‐β by avian retrovirus‐transformed lymphoid cells

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Abstract
The RRR‐α‐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‐β (TGF‐β) was established by 1) growth inhibition of TGF‐β‐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‐β, and 4) immunoprecipitation of metabolically labeled TGF‐β in CM from VES‐treated C4–1 cells by use of TGF‐β‐specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF‐β isoform‐specific mRNAs; namely, VES does not alter the levels of the 3.9‐ and 4.1‐kb TGF‐β2mRNAs, the 3.0‐kb TGF‐β3 mRNA, or the 2.5‐, 2.7‐, and 1.7‐kb TGF‐β4 mRNAs. The data show that VES inhibits C4–1 cell proliferation and induces the cells to produce and secrete active forms of TGF‐β, suggesting that one mechanism whereby VES inhibits C4–1 cell proliferation may be via the TGF‐β pathway for cellular growth control.