Abstract | BACKGROUND: METHODS: CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/ propidium iodide labeling. RESULTS: CONCLUSIONS: In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.
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Authors | Aintzane Apraiz, Jolanta K Idkowiak-Baldys, María Dolores Boyano, Gorka Pérez-Yarza, Yusuf A Hannun, Aintzane Asumendi |
Journal | BMC cancer
(BMC Cancer)
Vol. 11
Pg. 477
(Nov 07 2011)
ISSN: 1471-2407 [Electronic] England |
PMID | 22061047
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Sphingolipids
- Fenretinide
- Oxidoreductases
- dihydroceramide desaturase
- Sphingosine
- safingol
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Topics |
- Analysis of Variance
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Fenretinide
(pharmacology)
- Humans
- Leukemia
(drug therapy, metabolism)
- Oxidoreductases
(metabolism)
- Sphingolipids
(metabolism)
- Sphingosine
(analogs & derivatives, metabolism)
- Tumor Cells, Cultured
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