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 analysis, 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 treatment.
Charpentier
A
A
Division of Nutritional Sciences, University of Texas at Austin 78712-1097, USA.
Simmons-Menchaca
M
M
Yu
W
W
Zhao
B
B
Qian
M
M
Heim
K
K
Sanders
B G
BG
Kline
K
K
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D024505:Tocopherols; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D004247:DNA; D024505:Tocopherols