RRR-alpha-tocopheryl succinate induces MDA-MB-435 and MCF-7 human breast cancer cells to undergo differentiation.
Cell Growth Differ. 2001 Sep; 12(9):471-80.CG

Abstract

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.

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Authors+Show Affiliations

You H
School of Biological Sciences/C0900, University of Texas at Austin, Austin, Texas 78712, USA.
Yu W
No affiliation info available
Sanders BG
No affiliation info available
Kline K
No affiliation info available

MeSH

AntibodiesBiomarkersBreast NeoplasmsCaseinsCell DifferentiationCyclin D1Cytoskeletal ProteinsHumansIntercellular Adhesion Molecule-1JNK Mitogen-Activated Protein KinasesKeratinsLipid MetabolismMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeutralization TestsRNA, MessengerReceptor, ErbB-2Receptors, Cytoplasmic and NuclearSignal TransductionTocopherolsTrans-ActivatorsTranscription FactorsTransforming Growth Factor betaTumor Cells, CulturedVitamin Ebeta Catenin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11571230