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.
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Authors | Laura Emionite, Fabia Galmozzi, Myriam Grattarola, Francesco Boccardo, Laura Vergani, Salvatore Toma |
Journal | Anticancer research
(Anticancer Res)
2004 Nov-Dec
Vol. 24
Issue 6
Pg. 4019-24
ISSN: 0250-7005 [Print] Greece |
PMID | 15736447
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoates
- Chromans
- Enzyme Inhibitors
- Histone Deacetylase Inhibitors
- Histones
- Hydroxamic Acids
- Phenylbutyrates
- Ro 41-5253
- trichostatin A
- Tretinoin
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Topics |
- Acetylation
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Benzoates
(administration & dosage, pharmacology)
- Breast Neoplasms
(drug therapy, enzymology)
- Cell Line, Tumor
- Chromans
(administration & dosage, pharmacology)
- Drug Synergism
- Enzyme Inhibitors
(administration & dosage, pharmacology)
- Flow Cytometry
- Histone Deacetylase Inhibitors
- Histones
(metabolism)
- Humans
- Hydroxamic Acids
(administration & dosage, pharmacology)
- Phenylbutyrates
(administration & dosage)
- Tretinoin
(administration & dosage, pharmacology)
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