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-deace...

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Bibliographic Details
Published in:Anticancer research 2004-11, Vol.24 (6), p.4019-4024
Main Authors: EMIONITE, Laura, GALMOZZI, Fabia, GRATTAROLA, Myriam, BOCCARDO, Francesco, VERGANI, Laura, TOMA, Salvatore
Format: Article
Language:English
Subjects:
Acetylation
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Benzoates - administration & dosage
Benzoates - pharmacology
Biological and medical sciences
Breast Neoplasms - drug therapy
Breast Neoplasms - enzymology
Cell Line, Tumor
Chromans - administration & dosage
Chromans - pharmacology
Drug Synergism
Enzyme Inhibitors - administration & dosage
Enzyme Inhibitors - pharmacology
Flow Cytometry
Gynecology. Andrology. Obstetrics
Histone Deacetylase Inhibitors
Histones - metabolism
Humans
Hydroxamic Acids - administration & dosage
Hydroxamic Acids - pharmacology
Mammary gland diseases
Medical sciences
Phenylbutyrates - administration & dosage
Tretinoin - administration & dosage
Tretinoin - pharmacology
Tumors
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Summary: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.
ISSN:0250-7005
1791-7530