RRR-alpha-tocopheryl succinate enhances TGF-beta(1), -beta(2), and -beta(3) and TGF-beta R-II expression by human MDA-MB-435 breast cancer cells

The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM) from VES growth-inhibited cells contained potent antiproliferative activity, part of which is contributed by transforming growth factor-beta: (TGF-beta) isoforms. Antibody neutralization analyses, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta(1), -beta(2), and -beta(3) were present in the CM from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the levels of constitutively expressed 2.4-kb TGF-beta(1), 3.0- and 4.0-kb TGF-beta(2), or 1.2- and 3.5-kb TGF-beta(3) mRNA transcripts. Inhibition of DNA synthesis by MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and purified TGF-beta(1). VES-treated MDA-MB-435 cells exhibited enhanced binding of radiolabeled TGF-beta(1), and Western immunoblotting analyses showed that VES treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that biologically active TGF-beta(1), -beta(2), -beta(3) and levels of TGF-beta type II receptor expressed by human breast cancer cells are enhanced by VES treatments.