Arsenic trioxide, a therapeutic agent for APL
| Autor: | Zhen-Yi Wang, Sai-Juan Chen, Ting-Dong Zhang, Zhu-Gang Wang, Guo-Qiang Chen, Zhu Chen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Acute promyelocytic leukemia
Cancer Research Oncogene Proteins Fusion medicine.medical_treatment Cellular differentiation Antineoplastic Agents Apoptosis Tretinoin Promyelocytic Leukemia Protein Arsenicals Toxicology Promyelocytic leukemia protein chemistry.chemical_compound Mice Arsenic Trioxide Leukemia Promyelocytic Acute Antineoplastic Combined Chemotherapy Protocols Genetics medicine Animals Humans Arsenic trioxide Molecular Biology Chemotherapy biology Tumor Suppressor Proteins Remission Induction Nuclear Proteins Cell Differentiation Drug Synergism Oxides medicine.disease Mitochondria Neoplasm Proteins Survival Rate Leukemia Disease Models Animal chemistry Cancer research biology.protein medicine.drug Transcription Factors |
| Zdroj: | Oncogene. 20(49) |
| ISSN: | 0950-9232 |
| Popis: | Acute promyelocytic leukemia (APL) is an interesting model in cancer research, because it can respond to the differentiation/apoptosis induction therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). Over the past 5 years, it has been well demonstrated that As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed APL patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As(2)O(3) as post-remission therapy has given better survival than those treated with As(2)O(3) alone. The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 microM of As(2)O(3) while partial differentiation is observed using low concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the mechanisms underlying APL cell differentiation induced by low dose arsenic remain to be explored. Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately 2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as well as the wild-type PML, thus setting up a good example of targeting therapy for human cancers. |
| Databáze: | OpenAIRE |
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