N-(4-hydroxyphenyl)retinamide increases ceramide and is cytotoxic to acute lymphoblastic leukemia cell lines, but not to non-malignant lymphocytes
| Autor: | Peter H. O'Donnell, Reynolds Cp, Guo Wx, Barry J. Maurer |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Ceramide Time Factors Fenretinide Cell Survival Morpholines Antineoplastic Agents Biology Ceramides Peripheral blood mononuclear cell chemistry.chemical_compound Null cell Tumor Cells Cultured Cytotoxic T cell Humans Lymphocytes Cytotoxicity Sphingolipids Dose-Response Relationship Drug Drug Synergism Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Sphingolipid Molecular biology Oncology chemistry Biochemistry Cell culture |
| Zdroj: | Leukemia. 16(5) |
| ISSN: | 0887-6924 |
| Popis: | The retinoid, N-(4-hydroxyphenyl)retinamide (4-HPR), mediates p53-independent cytotoxicity and can increase reactive oxygen species and ceramide in solid tumor cell lines. We determined changes in ceramide and cytotoxicity upon treatment with 4-HPR (3-12 microM) in six human acute lymphoblastic leukemia (ALL) cell lines: T cell (MOLT-3, MOLT-4, CEM), pre-B-cell (NALM-6, SMS-SB), and null cell (NALL-1). Exposure to 4-HPR (12 microM) for 96 h caused 4.7 (MOLT-3), 3.5 (MOLT-4), 3.9 (CEM), 2.9 (NALM-6), 4.7 (SMS-SB), AND 4.5 (NALL-1) logs of cell kill. The average 4-HPR concentration that killed 99% of cells (LC(99)) for all six lines was 4.8 microM (range: 1.5-8.9 microM). Treatment with 4-HPR (9 microM) for 24 h resulted in an 8.9 +/- 1.0-fold (range: 4.9-15.7-fold) increase of ceramide. Ceramide increase was time- and dose-dependent and abrogated by inhibitors of de novo ceramide synthesis. Concurrent inhibition of ceramide glycosylation/acylation by d,l-threo-(1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol) (PPMP) further increased ceramide levels, and synergistically increased 4-HPR cytotoxicity in four of six ALL cell lines. 4-HPR was minimally cytotoxic to peripheral blood mononuclear cells and a lymphoblastoid cell line, and increased ceramide |
| Databáze: | OpenAIRE |
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