title: L-asparaginase induces in AML U937 cells apoptosis via an AIF-mediated mechanism.
abstract: Acute Myeloid Leukemia (AML), a cancer of the myeloid line of blood cells, progresses rapidly and is typically fatal within weeks or months if left untreated. Asparaginases are a class of enzymatic anti-leukemia agents that induce apoptosis in leukemia cell lines; however, the role of L-asparaginase in the induction of apoptosis in AML cells has not been investigated. In this study, we investigated the apoptosis-inducing effect of L-asparaginase and its underlying mechanism in AML U937 cells. The results showed that L-asparaginase significantly inhibited the proliferation of U937 cells by inducing apoptosis. Furthermore, the low baseline expression level of asparaginase synthase (ASNS) demonstrated the sensitivity of U937 cells and AML M5, a rare subtype of AML, to L-asparaginase. Apoptosis induced by L-asparaginase is mediated by apoptosis-inducing factor (AIF). Our findings show the potential of L-asparaginase as an effective approach in treating AML via the induction of apoptosis mediated by AIF.
authors.affiliation: Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical College,Guangzhou, 510623, China.
authors.forename: Yingyi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Benshang
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of , Children's Hospital of Shanghai, Shanghai Jiao Tong University, 200040, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Changying
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
authors.forename: Longjun
authors.initials: L
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000502:physiology*; D001215:Asparaginase / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D015996:Survival Rate; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D017931:DNA Primers; D001215:Asparaginase