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In fact, the use of synthetic aromatase inhibitors (AI), which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds <jats:bold>3a<\/jats:bold> and <jats:bold>4a<\/jats:bold>, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The new steroids inhibit hormone-dependent proliferation of MCF-7aro cells in a time and dose-dependent manner, causing cell cycle arrest in G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> phase and inducing cell death with features of apoptosis and autophagic cell death.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our <jats:italic>in vitro<\/jats:italic> studies showed that the two steroidal AIs, <jats:bold>3a<\/jats:bold> and <jats:bold>4a<\/jats:bold>, are potent inhibitors of breast cancer cell proliferation. Moreover, it was also shown that the antiproliferative effects of these two steroids on MCF-7aro cells are mediated by disrupting cell cycle progression, through cell cycle arrest in G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> phase and induction of cell death, being the dominant mechanism autophagic cell death. Our results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2121-9-41","type":"journal-article","created":{"date-parts":[[2008,7,24]],"date-time":"2008-07-24T18:13:48Z","timestamp":1216923228000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["New steroidal aromatase inhibitors: Suppression of estrogen-dependent breast cancer cell proliferation and induction of cell death"],"prefix":"10.1186","volume":"9","author":[{"given":"Margarida","family":"Cepa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisi\u00e1rio J Tavares","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda MF","family":"Roleira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarida","family":"Borges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e9rcia A","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,7,24]]},"reference":[{"key":"319_CR1","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1210\/jcem-38-3-476","volume":"38","author":"DL Hemsell","year":"1974","unstructured":"Hemsell DL, Grodin J, Breuner PF: Plasma precursors of estrogen. 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