Upregulation of Bfl-1/A1 in leukemia cells undergoing differentiation by all-trans retinoic acid treatment attenuates chemotherapeutic agent-induced apoptosis
| Autor: | E Wurmbach, Samuel Waxman, Yongkui Jing, Lijuan Xia |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Acute promyelocytic leukemia
Cancer Research Programmed cell death Paclitaxel medicine.drug_class Cellular differentiation Retinoic acid Antineoplastic Agents Apoptosis HL-60 Cells Tretinoin Biology Arsenicals Minor Histocompatibility Antigens chemistry.chemical_compound Downregulation and upregulation Arsenic Trioxide Cell Line Tumor medicine Humans Retinoid Gene Silencing RNA Small Interfering Cell Proliferation Leukemia Dose-Response Relationship Drug Cell Differentiation Oxides Hematology medicine.disease Up-Regulation Oncology chemistry Proto-Oncogene Proteins c-bcl-2 Doxorubicin Cancer research medicine.drug |
| Zdroj: | Leukemia. 20(6) |
| ISSN: | 0887-6924 |
| Popis: | All-trans retinoic acid (ATRA) induces differentiation of NB4 and HL-60 leukemia cells, but not R4 and HL-60/Res cells. Three agents used in cancer therapy, doxorubicin (Dox), arsenic trioxide (As(2)O(3)) and paclitaxel, induce apoptosis, but not differentiation, in all of these cell lines. The induction of apoptosis by these agents is decreased in ATRA-pretreated NB4 and HL-60 cells, but not in ATRA-pretreated R4 and HL-60/Res cells. The level of Bcl-2 protein is decreased by ATRA treatment in NB4, HL-60 and HL-60/Res cells. The level of Mcl-1 protein is increased by ATRA treatment in NB4 and R4 cells, but not in HL-60 and HL-60/Res cells. Bfl-1/A1 mRNA is not expressed in these cell lines, however, its expression is markedly induced by ATRA treatment in NB4 and HL-60 cells, but not in R4 or HL-60/Res cells, which correlates with inhibition of apoptosis. Inhibiting Bfl-1/A1 mRNA upregulation in ATRA-pretreated NB4 cells using small interfering RNA (siRNA) partly recovers cell sensitivity to Dox-induced apoptosis. These data demonstrate that ATRA induction of Bfl-1/A1 in differentiated NB4 and HL-60 cells contributes to a loss of sensitivity to chemotherapy-induced apoptosis. |
| Databáze: | OpenAIRE |
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