VITAMIN-E SUCCINATE INDUCES FAS-MEDIATED APOPTOSIS IN ESTROGEN RECEPTOR-NEGATIVE HUMAN BREAST-CANCER CELLS

Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-a lpha-tocopherol (vitamin E), inhibited growth and induced apoptotic ce ll death of estrogen receptor-negative human breast cancer cells, VES- induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fa s 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 a poptosis, The presence of Fas-L antisense oligonucleotides also comple tely blocked the VES-mediated increase in Fas-L protein expression. Th ese data indicate a role for Fas signaling in VES-mediated apoptotic c ell death of human breast cancer cells. These findings also suggest th at VES may be of clinical use in the treatment of aggressive human bre ast cancers, particularly those that are refractory to antiestrogen th erapy.