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Vitamin E Succinate Induces Fas-mediated Apoptosis in Estrogen Receptor-Negative Human Breast Cancer Cells¹

Laboratory of Leukocyte Biology, Division of Basic Sciences, National Cancer Institute, Frederick, Maryland 21702 [J. M. T., F. W. R.] and Intramural Research Support Program, Science Applications International Corporation (SAIC)-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [T. F., J. A. M., D. C. B., M. C. B-R.]

Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D--tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells. VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway. Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas ligand (Fas-L) were increased following VES treatment. In addition, VES increased cell surface Fas expression. Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis. The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy.

¹ The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

² To whom requests for reprints should be addressed, at Laboratory of Leukocyte Biology, Building 567, Room 276, National Cancer Institute, Frederick, MD 21702. Phone: (301) 846-1442; Fax: (301) 846-7034.

Received 8/ 9/96. Accepted 1/ 2/97.

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