title: Could in-vitro studies on Ishikawa cell lines explain the endometrial safety of raloxifene? Systematic literature review and starting points for future oncological research.
abstract: To evaluate all the in-vitro raloxifene (RAL) mechanisms of action on normal, Ishikawa, and different endometrium-derived cell lines to explain the in-vivo RAL endometrial effects, a systematic literature search was performed in the electronic databases MEDLINE, EMBASE ScienceDirect, and the Cochrane Library for the time period between 2002 and 2012. Outcomes were considered in relation to in-vitro stimulatory, inhibitory, or neutral actions of RAL in Ishikawa cell lines compared with different endometrial-derived cell lines (both cancerous and normal endometrium). We also considered all the RAL molecular mechanisms responsible for the in-vitro effects observed. More than 150 articles were available in the scientific database literature, but only 21 fulfilled our selection criteria. Although in-vitro studies appear to yield conflicting results, most evidence has shown that RAL seems to induce endometrial cell mitochondria-mediated apoptosis, and to inhibit estrogen-related cell proliferation and endometrial carcinogenesis by inducing antiangiogenic factors, and reducing cytoskeletal reorganization. If the endometrial safety profile of RAL is confirmed, in the near future, selective estrogen receptor modulators could represent an efficient alternative adjuvant treatment to tamoxifen (TAM) in women with breast cancer considered to be at an increased risk of endometrial disease. The confirmation of the endometrial safety profile could enable the proposal of RAL by clinicians as the most appropriate treatment for BRCA1-2 patients after prophylactic salpingo-oophorectomy.
authors.affiliation: Department of Woman and Child Health, University of Padua, Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gizzo
authors.forename: Marco
authors.initials: M
authors.lastname: Noventa
authors.forename: Stefania
authors.initials: S
authors.lastname: Di Gangi
authors.forename: Pietro
authors.initials: P
authors.lastname: Litta
authors.forename: Carlo
authors.initials: C
authors.lastname: Saccardi
authors.forename: Donato
authors.initials: D
authors.lastname: D'Antona
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Nardelli
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
chemical_list: D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride