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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

Changes in the protein expression levels of EVI-1, JNK, p-JNK, Bcl-2, Bcl-xL, Bax, full-length caspase-3 and cleaved caspase-3 in the THP1 cell line treated with ATO at various concentrations. Representative western blot results are shown. Results are expressed as the mean ± standard deviation (n=3). *P<0.01, vs. control group. EVI-1, ecotropic viral integration site-1; JNK, c-Jun N-terminal kinase; p-JNK, phosphorylated JNK; Bcl-2, B-cell lymphoma 2; Bcl-xL, B-cell lymphoma-extra large; ATO, arsenic trioxide.
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f5-etm-08-01-0085: Changes in the protein expression levels of EVI-1, JNK, p-JNK, Bcl-2, Bcl-xL, Bax, full-length caspase-3 and cleaved caspase-3 in the THP1 cell line treated with ATO at various concentrations. Representative western blot results are shown. Results are expressed as the mean ± standard deviation (n=3). *P<0.01, vs. control group. EVI-1, ecotropic viral integration site-1; JNK, c-Jun N-terminal kinase; p-JNK, phosphorylated JNK; Bcl-2, B-cell lymphoma 2; Bcl-xL, B-cell lymphoma-extra large; ATO, arsenic trioxide.

Mentions: RT-PCR and western blotting were used to detect the expression levels of EVI-1 mRNA and protein, respectively, in THP1 cells treated with various concentrations of ATO (0, 1, 3 and 5 μM) for 24, 48 and 72 h. Exposure to increasing concentrations of ATO for increasing lengths of time was associated with gradual inhibition in the expression of EVI-1 mRNA (Fig. 4) and protein (Fig. 5).


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)

Changes in the protein expression levels of EVI-1, JNK, p-JNK, Bcl-2, Bcl-xL, Bax, full-length caspase-3 and cleaved caspase-3 in the THP1 cell line treated with ATO at various concentrations. Representative western blot results are shown. Results are expressed as the mean ± standard deviation (n=3). *P<0.01, vs. control group. EVI-1, ecotropic viral integration site-1; JNK, c-Jun N-terminal kinase; p-JNK, phosphorylated JNK; Bcl-2, B-cell lymphoma 2; Bcl-xL, B-cell lymphoma-extra large; ATO, arsenic trioxide.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-etm-08-01-0085: Changes in the protein expression levels of EVI-1, JNK, p-JNK, Bcl-2, Bcl-xL, Bax, full-length caspase-3 and cleaved caspase-3 in the THP1 cell line treated with ATO at various concentrations. Representative western blot results are shown. Results are expressed as the mean ± standard deviation (n=3). *P<0.01, vs. control group. EVI-1, ecotropic viral integration site-1; JNK, c-Jun N-terminal kinase; p-JNK, phosphorylated JNK; Bcl-2, B-cell lymphoma 2; Bcl-xL, B-cell lymphoma-extra large; ATO, arsenic trioxide.
Mentions: RT-PCR and western blotting were used to detect the expression levels of EVI-1 mRNA and protein, respectively, in THP1 cells treated with various concentrations of ATO (0, 1, 3 and 5 μM) for 24, 48 and 72 h. Exposure to increasing concentrations of ATO for increasing lengths of time was associated with gradual inhibition in the expression of EVI-1 mRNA (Fig. 4) and protein (Fig. 5).

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