The promoting action of E2 in breast cancer cells has been, until now, main
ly linked to its action on prolifieration. Because of the importance of an
increase in apoptosis in breast cancer prevention, we have studied the poss
ible effects of various antiestrogens, progestins and an androgen on its oc
currence in three hormone-dependent breast cancer cell lines. The antiestro
gens were, a triphenylethylene derivative, 4 hydroxytamoxifen(4OHTAM) and t
wo steroidal antiestrogens, ICI182780 and RU58668. The progestins were Org2
058, a pregnane derivative, tibolone (OrgOD14), a normethyltestosterone der
ivative and OrgOM38 (the Delta 4 isomer of OrgOD14) and the androgen dihydr
otestosterone (DHT). Apoptosis was studied in MCF-7, ZR75-1 and T47-D cells
using morphological approaches and flow cytometry, The antiestrogens, the
progestins and DHT were proapoptotic but to different potencies according t
o the cell line studied. Indeed, the 'pure' steroidal antiestrogens were mo
re efficient than 4OHTam in increasing apoptosis. We have also studied the
level of expression of some of the proteins involved in the regulation of a
poptosis. Bcl-2 and bcx(L), two antiapoptotic members of the bcl-2 family p
roteins, were inhibited by the progestins and the antiestrogens. In contras
t, the proapoptotic proteins, bar and bak seemed to be constitutively expre
ssed. Thus, since the ratio of proapoptotic and antiapoptotic proteins dete
rmines apoptosis or cell survival, the hormone effects are operating by mod
ulating the antiapoptotic regulators of the balance. These data demonstrate
that antiestrogens, progestins, and androgens can promote apoptosis in bre
ast cancer cells, an effect which could be of importance in the therapeutic
prevention of breast cancer. (C) 1999 Elsevier Science Ltd. All rights res
erved.