Tibolone actions on normal and breast cancer cells

Citation
A. Gompel et al., Tibolone actions on normal and breast cancer cells, EUR J CANC, 36, 2000, pp. S76-S77
Citations number
4
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
EUROPEAN JOURNAL OF CANCER
ISSN journal
09598049 → ACNP
Volume
36
Year of publication
2000
Supplement
4
Pages
S76 - S77
Database
ISI
SICI code
0959-8049(200009)36:<S76:TAONAB>2.0.ZU;2-3
Abstract
Tibolone and its main derivatives were studied in an original model of cult ures of normal human epithelial breast (HBE) cells on proliferation, differ entation and apoptosis, the three mechanisms responsible for breast homeost asis. Tibolone and its Delta4 isomer were antiproliferative, both in the ab sence and presence of oestradiol (E2). The oestrogenic 3 alpha and 3 beta h ydroxy derivatives did not display any mitogenic activities in HBE cells. M oreover, at 1 muM, they were antiproliferative. Tibolone and its Delta isom er increased the 17 beta hydroxysteroid dehydrogenase activity similarly to that observed with progestins [1]. Apoptosis was increased in HBE cells to a similar range as with the pure pregnane progestin, Org2058. We also stud ied the extent of apoptosis in hormone-dependent breast cancer cell lines. Tibolone and its Delta4 isomer also increased apoptosis, especially in ZR75 -1 cells containing progesterone and androgen receptors [2]. We could demon strate that these pro-apoptotic actions of tibolone and its Delta4 isomer w ere mediated at least partially through the bcl-2-family of proteins. Moreo ver, the antiproliferative and pro-apoptotic activities of tibolone, as wel l as Org2058, were mediated by increasing catalase activities in breast can cer cells. Thus, in breast cells, tibolone slows down the proliferation rat e, increases differentiation and apoptosis. These actions seem to be optima l on breast tissue. (C) 2000 Elsevier Science Ltd. All rights reserved.