Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude mice.
|
| Abstract |
EM-652 exerts pure antiestrogenic activity in the mammary gland and endometrium, while tamoxifen, the antiestrogen most widely used for the treatment of breast cancer, exerts mixed antiestrogenic-estrogenic activity in these tissues. Our objective was to compare the agonistic and antagonistic effects of EM-652 with tamoxifen and 5 other antiestrogens on the growth of ZR-75-1 human breast xenografts in ovariectomized nude mice. During the 23 weeks of treatment at a daily oral dose of 50 microg, EM-652 was the only compound that decreased tumor size relative to pretreatment values, whereas the 6 other antiestrogens only decreased to various extents the progression rate stimulated by estrone. Under estrone stimulation, all groups of animals had more than 60% of their tumors in the progression category except for the EM-652-treated group, where only 7% of the tumors progressed. In the absence of estrone stimulation, progression was seen in 60%, 33%, 21% and 12% of tumors in the tamoxifen-, idoxifene-, toremifene- and raloxifene-treated groups, respectively, while only 4% of tumors progressed in the EM-652-treated group. The agonistic and antagonistic actions of each antiestrogen were also measured on endometrial epithelial cell thickness. Our present findings indicate that EM-652, in addition to being the most potent antiestrogen on human breast tumor growth, has no agonistic effect in breast and endometrial tissues. Since previous data have shown benefits of EM-652 on bone density and lipid profile, this compound could be an ideal candidate for chemoprevention of breast and uterine cancers, while protecting against osteoporosis and cardiovascular disease.
|
|---|---|
| Authors | Matthieu Gutman, Steeve Couillard, Jenny Roy, Fernand Labrie, Bernard Candas, Claude Labrie |
| Journal | International journal of cancer (Int J Cancer) Vol. 99 Issue 2 Pg. 273-8 (May 10 2002) ISSN: 0020-7136 [Print] United States |
| PMID | 11979444 (Publication Type: Comparative Study, Journal Article) |
| Copyright | Copyright 2002 Wiley-Liss, Inc. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!