title: Arsenic trioxide induces apoptosis in the THP1 cell line by downregulating EVI-1.
abstract: Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the current study, the effects of arsenic trioxide (ATO) on the ecotropic viral integration site-1 (EVI-1) gene were investigated in the THP1 cell line. THP-1 cells were treated with different concentrations of ATO (0, 1, 3 and 5 μM) for 24, 48 or 72 h, then tested for cell viability by CCK-8 kit, cell morphology by cytospin smear, cell apoptosis by flow cytometry, EVI-1 mRNA expression by reverse transcription polymerase chain reaction (RT-PCR) and protein quantity by western blot. ATO treatment was shown to inhibit proliferation and induce apoptosis in THP1 cells in a dose- and time-dependent manner. ATO downregulated the mRNA and protein expression of EVI-1 in the THP1 cell line. In addition, ATO significantly decreased the expression of antiapoptotic proteins, B-cell lymphoma 2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), but markedly increased the expression of proapoptotic proteins, including c-Jun N-terminal kinase (JNK), phosphorylated-JNK, Bax, full length caspase-3 and cleaved caspase-3. These results indicated that ATO inhibited the proliferation and induced apoptosis in THP1 cells partially via blocking the inhibitory effects of EVI-1 on the JNK signaling pathway with the involvement of apoptosis-associated proteins, including Bax, Bcl-2, Bcl-xL and caspase-3. These novel observations may be used to elucidate the mechanism by which ATO induces apoptosis in acute leukemia cells, and provide rationales to develop a personalized medicine strategy for ATO via targeting EVI-1 positive neoplasm.
authors.affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Chen
authors.affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Shen
authors.affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Wan
authors.affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Zhong
keywords: THP1; apoptosis; arsenic trioxide; ecotropic viral integration site-1