Induction of apoptosis via the modulation of reactive oxygen species (ROS) production in the treatment of myeloid leukemia.
Recent advances in genetic and molecular biology have provided greater insight into the biology of acute myeloid leukemia (AML). These investigations have shown that AML is a heterogeneous disease of biologically different entities. Current therapeutic approaches to AML are based on chemotherapy, but the side effects of the drugs used and various complications, including infections and bleeding, are sometimes fatal. In addition, responses to therapy and long-term outcome differ depending on the subentity in question. Therefore, it is essential to develop new therapeutic strategies such as biology adapted treatment based on the individual molecular pathogenesis of AML. Natural compounds appear to be safer than the current chemotherapeutic drugs, and we have therefore sought new potential agents among various natural compounds with the ability to induce the apoptosis of myeloid leukemic cells. Recently, we found that a highly toxic reactive oxygen species (ROS) generated via the hydrogen peroxide/myeloperoxidase [H(2)O(2)/MPO/halide] system by natural compounds induces apoptosis in MPO-positive leukemic cells. This result is of great interest in establishing novel therapeutic approaches to AML mediated through ROS-induced apoptosis of leukemic cells.
Kizaki
Masahiro
M
Division of Hematology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. makizaki@sc.itc.keio.ac.jp
Xian
Mingji
M
Sagawa
Morihiko
M
Ikeda
Yasuo
Y
D000970:Antineoplastic Agents / Q000008:administration & dosage; D001059:Apoproteins / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D001059:Apoproteins; D017382:Reactive Oxygen Species