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Arsenic trioxide induces apoptosis in the THP1 cell line by downregulating EVI-1.

Zhou LY, Chen FY, Shen LJ, Wan HX, Zhong JH - Exp Ther Med (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

Inhibitory effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01). Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.
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f2-etm-08-01-0085: Inhibitory effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01). Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.

Mentions: CCK-8 was used to analyze the effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01; Fig. 2). The 48-h IC50 value for ATO in the THP1 cells was determined as 2.99±0.09 μM.


Arsenic trioxide induces apoptosis in the THP1 cell line by downregulating EVI-1.

Zhou LY, Chen FY, Shen LJ, Wan HX, Zhong JH - Exp Ther Med (2014)

Inhibitory effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01). Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061239&req=5

f2-etm-08-01-0085: Inhibitory effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01). Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.
Mentions: CCK-8 was used to analyze the effect of ATO on the viability of the THP1 cell line. The growth of THP1 cells was inhibited by ATO in a dose- and time-dependent manner (two-way analysis of variance, P<0.01; Fig. 2). The 48-h IC50 value for ATO in the THP1 cells was determined as 2.99±0.09 μM.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus