Interaction between arsenic trioxide and human primary cells: emphasis on human cells of myeloid origin.
Arsenic trioxide (As(2)O(3); ATO) is considered to be one of the most potent drugs in cancer chemotherapy and is highly effective in the treatment of acute promyelocytic leukemia (APL). It is well established that treatment of APL patients with ATO is associated with the disappearance of the PML-RARalpha fusion transcript, the characteristic APL gene product of the chromosomal translocation t(15;17). Although its mode of action is still not fully understood, ATO is known to induce cell apoptosis via generation of reactive oxygen species and activation of caspases. Several reports have indicated that ATO acts principally by inducing cell apoptosis not only in APL, but in a variety of non-APL cells including myeloma cells, chronic myeloid leukemia cells and cells of immune origin, including B or T lymphocytes, macrophages and, more recently, neutrophils. There is an increasing amount of data, including some from our laboratory, concerning the interaction between ATO and human primary cells. The focus of this review will be to cover the role of ATO in human immune primary cells with special emphasis on cells of myeloid origin.
Binet
François
F
Université du Québec, INRS-Institut Armand-Frappier, QC, Canada.
Antoine
Francis
F
Girard
Denis
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D015550:Cell Degranulation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System; D022423:Myeloid Cells / Q000187:drug effects* / Q000502:physiology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D000077237:Arsenic Trioxide