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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

Induction of apoptosis by ATO in the THP1 cell line. (A) Morphological changes in the THP1 cell line treated with ATO were observed using light microscopy (hematoxylin and eosin staining; magnification, ×1,000). Compared with the control group, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, including a large number of bubbles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies. (B) Fluorescence-activated cell sorting analysis was conducted to analyze the apoptosis rate induced by ATO in THP1 cells. *P<0.05, vs. previous concentration at the same time point; #P<0.05, vs. previous time point at the same concentration. Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.
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f3-etm-08-01-0085: Induction of apoptosis by ATO in the THP1 cell line. (A) Morphological changes in the THP1 cell line treated with ATO were observed using light microscopy (hematoxylin and eosin staining; magnification, ×1,000). Compared with the control group, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, including a large number of bubbles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies. (B) Fluorescence-activated cell sorting analysis was conducted to analyze the apoptosis rate induced by ATO in THP1 cells. *P<0.05, vs. previous concentration at the same time point; #P<0.05, vs. previous time point at the same concentration. Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.

Mentions: Compared with the control groups, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, as observed in the light microscope images. Observations included a large number of vacuoles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies (Fig. 3).


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)

Induction of apoptosis by ATO in the THP1 cell line. (A) Morphological changes in the THP1 cell line treated with ATO were observed using light microscopy (hematoxylin and eosin staining; magnification, ×1,000). Compared with the control group, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, including a large number of bubbles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies. (B) Fluorescence-activated cell sorting analysis was conducted to analyze the apoptosis rate induced by ATO in THP1 cells. *P<0.05, vs. previous concentration at the same time point; #P<0.05, vs. previous time point at the same concentration. 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

f3-etm-08-01-0085: Induction of apoptosis by ATO in the THP1 cell line. (A) Morphological changes in the THP1 cell line treated with ATO were observed using light microscopy (hematoxylin and eosin staining; magnification, ×1,000). Compared with the control group, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, including a large number of bubbles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies. (B) Fluorescence-activated cell sorting analysis was conducted to analyze the apoptosis rate induced by ATO in THP1 cells. *P<0.05, vs. previous concentration at the same time point; #P<0.05, vs. previous time point at the same concentration. Results are expressed as the mean ± standard deviation (n=3). ATO, arsenic trioxide.
Mentions: Compared with the control groups, cells treated with 3 μM ATO for 24, 48 and 72 h exhibited typical apoptotic characteristics, as observed in the light microscope images. Observations included a large number of vacuoles in the cytoplasm, higher intensity of nuclear staining, karyopyknosis and the formation of crescents and apoptotic bodies (Fig. 3).

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