Histone deacetylase inhibitors enhance retinoid response in human breast cancer cell lines.
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.
Emionite
Laura
L
Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy.
Galmozzi
Fabia
F
Grattarola
Myriam
M
Boccardo
Francesco
F
Vergani
Laura
L
Toma
Salvatore
S
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
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