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.
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.
Simmons-Menchaca
M
M
Genetics Institute, University of Texas at Austin 78712-1097, USA.
Qian
M
M
Yu
W
W
Sanders
B G
BG
Kline
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001717:Birds; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae; D024505:Tocopherols; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D024505:Tocopherols