title: Histone deacetylase inhibitors enhance retinoid response in human breast cancer cell lines.
abstract: Solid tumors develop resistance to retinoids during carcinogenesis. One of the strategies to overcome this resistance may include the combination of these molecules with other differentiating, cytotoxic or chromatin-remodelling agents. We analysed the anti-proliferative activity of two histone-deacetylase inhibitors (HDACIs), Trichostatin A (TSA) and sodium phenylbutyrate (PB), alone or combined with retinoids, all-trans retinoic acid (ATRA) and Ro 41-5253, on two human breast cancer cell lines: the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231. These lines responded differently to retinoids: MCF-7 were sensitive, whilst MDA-MB-231 were rather resistant. When the retinoids were combined with HDACIs, these molecules potentiated the retinoid activity on growth inhibition, especially for the association Ro 41-5253 and TSA. By FACS analysis, we observed that the anti-proliferative effects were only partially due to pro-apopotic mechanisms, suggesting a cell-cycle block. The efficacy of the retinoids/HDACIs combinations could represent a new strategy in breast cancer chemotherapy, allowing inhibition of both ER + and ER- cell populations.
authors.affiliation: Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Emionite
authors.forename: Fabia
authors.initials: F
authors.lastname: Galmozzi
authors.forename: Myriam
authors.initials: M
authors.lastname: Grattarola
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
authors.forename: Salvatore
authors.initials: S
authors.lastname: Toma
mesh_terms: D000107:Acetylation; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000008:administration & dosage*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001565:Benzoates; D002839:Chromans; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D010654:Phenylbutyrates; C084904:Ro 41-5253; C012589:trichostatin A; D014212:Tretinoin