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ABSTRACT: RRR-alpha-Tocopheryl Succinate Induces MDA-MB-435 and
MCF-7 Human Breast Cancer Cells to Undergo Differentiation
[10/04/2001; Cell Growth and Differentation]
RRR-alpha-Tocopheryl succinate (vitamin E succinate, VES) is a potent
antitumor agent, inducing DNA synthesis arrest, differentiation,
and apoptosis. Because little is known about VES-induced differentiation,
studies reported here characterize VES effects on the differentiation
status of human breast cancer cell lines and investigate possible
molecular mechanisms involved.
VES-induced differentiation of
human MCF-7 and MDA-MB-435 breast cancer cells was characterized
by morphological changes, induction of lipid droplets, induction
of beta-casein mRNA expression, and down-regulation of Her2/neu
protein.
In contrast, VES treatment of normal human mammary epithelial
cells, MCF-10A cells, and T-47D cells did not induce differentiation.
Studies addressing mechanisms showed that neither antibody neutralization
of the transforming growth factor-beta signaling pathway nor
expression of a dominant-negative mutant of c-Jun N-terminal
kinase blocked the ability of VES to induce differentiation;
however, treatment of cells with PD 98059, a chemical inhibitor
of mitogen-activated protein kinase kinase (MEK1/2), blocked
the ability of VES to induce differentiation.
Cell Growth and Differentiation
10/04/01
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