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Trans-1,3-diphenyl-2,3-epoxypropan-1-one, a chalcone derivative, induces apoptosis via ROS-mediated down-regulation of Bcl-xL in human leukemia HL-60 cells.

Ko EY, Lee SH, Ko JY, Moon JY, Yoon WJ, Ahn G, Roh SW, Cho K, Jeon YJ, Kim D, Kim KN - EXCLI J (2015)

Bottom Line: Treatment of HL-60 cells with various concentration of DPEP resulted in a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, and increased sub-G1 DNA content.However, NAC pre-treatment significantly inhibited the activation of caspase-3 and PARP cleavage and reduced Bcl-xL levels.These findings provide the first evidence that DPEP may inhibit the growth of HL-60 cells and induce apoptosis through a ROS-mediated Bcl-xL pathway.

View Article: PubMed Central - PubMed

Affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea; School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.

ABSTRACT
The anticancer effects of trans-1,3-diphenyl-2,3-epoxypropan-1-one (DPEP), a chalcone derivative, were investigated in human leukemia HL-60 cells. Treatment of HL-60 cells with various concentration of DPEP resulted in a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, and increased sub-G1 DNA content. We demonstrated that DPEP elevates reactive oxygen species (ROS) levels in HL-60 cells, and that the ROS scavenger N-acetylcysteine (NAC) could block DPEP-induced ROS generation and apoptosis. Western blot analysis revealed that DPEP inhibits Bcl-xL expression, leading to caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, thereby inducing apoptosis. However, NAC pre-treatment significantly inhibited the activation of caspase-3 and PARP cleavage and reduced Bcl-xL levels. These findings provide the first evidence that DPEP may inhibit the growth of HL-60 cells and induce apoptosis through a ROS-mediated Bcl-xL pathway.

No MeSH data available.


Related in: MedlinePlus

Induction of apoptosis by the DPEP treatment of HL-60 cells. HL-60 cells were seeded at 2 × 105 cells/mL and treated with different DPEP concentrations for 12 h. (A) Apoptotic bodies were stained with Hoechst 33342 solution and observed under a fluorescent microscope using blue filter. (B) The cells were stained with PI and analyzed via flow cytometry. The experiment was repeated three independent times.
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Figure 2: Induction of apoptosis by the DPEP treatment of HL-60 cells. HL-60 cells were seeded at 2 × 105 cells/mL and treated with different DPEP concentrations for 12 h. (A) Apoptotic bodies were stained with Hoechst 33342 solution and observed under a fluorescent microscope using blue filter. (B) The cells were stained with PI and analyzed via flow cytometry. The experiment was repeated three independent times.

Mentions: In order to determine whether the inhibitory effect of DPEP on cell viability was due to apoptosis, the HL-60 cells were treated with DPEP for 12 h, and Hoechst 33342 staining was performed. The controls, without DPEP exposure, exhibited no DNA damage (Figure 2A(Fig. 2)). However, obvious cell damage was observed in the DPEP-exposed cells. Cells treated with varying concentrations of DPEP (20, 30, and 40 μM) exhibited a dramatic increase in the number of apoptotic bodies (Figure 2A(Fig. 2)). Additionally, we measured the number of cells with sub-G1 DNA content, which is hypothesized to be apoptotic DNA, using flow cytometry. As shown in Figure 2B(Fig. 2), DPEP exposure increased the apoptotic portion of sub-G1 peaks in a dose-dependent manner (8.9 %, 45.3 %, and 53.3 % at concentrations of 20, 30, and 40 μM, respectively). Thus, apoptosis is correlated with the inhibition of cell growth, suggesting that HL-60 cells may undergo apoptosis after DPEP treatment.


Trans-1,3-diphenyl-2,3-epoxypropan-1-one, a chalcone derivative, induces apoptosis via ROS-mediated down-regulation of Bcl-xL in human leukemia HL-60 cells.

Ko EY, Lee SH, Ko JY, Moon JY, Yoon WJ, Ahn G, Roh SW, Cho K, Jeon YJ, Kim D, Kim KN - EXCLI J (2015)

Induction of apoptosis by the DPEP treatment of HL-60 cells. HL-60 cells were seeded at 2 × 105 cells/mL and treated with different DPEP concentrations for 12 h. (A) Apoptotic bodies were stained with Hoechst 33342 solution and observed under a fluorescent microscope using blue filter. (B) The cells were stained with PI and analyzed via flow cytometry. The experiment was repeated three independent times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834817&req=5

Figure 2: Induction of apoptosis by the DPEP treatment of HL-60 cells. HL-60 cells were seeded at 2 × 105 cells/mL and treated with different DPEP concentrations for 12 h. (A) Apoptotic bodies were stained with Hoechst 33342 solution and observed under a fluorescent microscope using blue filter. (B) The cells were stained with PI and analyzed via flow cytometry. The experiment was repeated three independent times.
Mentions: In order to determine whether the inhibitory effect of DPEP on cell viability was due to apoptosis, the HL-60 cells were treated with DPEP for 12 h, and Hoechst 33342 staining was performed. The controls, without DPEP exposure, exhibited no DNA damage (Figure 2A(Fig. 2)). However, obvious cell damage was observed in the DPEP-exposed cells. Cells treated with varying concentrations of DPEP (20, 30, and 40 μM) exhibited a dramatic increase in the number of apoptotic bodies (Figure 2A(Fig. 2)). Additionally, we measured the number of cells with sub-G1 DNA content, which is hypothesized to be apoptotic DNA, using flow cytometry. As shown in Figure 2B(Fig. 2), DPEP exposure increased the apoptotic portion of sub-G1 peaks in a dose-dependent manner (8.9 %, 45.3 %, and 53.3 % at concentrations of 20, 30, and 40 μM, respectively). Thus, apoptosis is correlated with the inhibition of cell growth, suggesting that HL-60 cells may undergo apoptosis after DPEP treatment.

Bottom Line: Treatment of HL-60 cells with various concentration of DPEP resulted in a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, and increased sub-G1 DNA content.However, NAC pre-treatment significantly inhibited the activation of caspase-3 and PARP cleavage and reduced Bcl-xL levels.These findings provide the first evidence that DPEP may inhibit the growth of HL-60 cells and induce apoptosis through a ROS-mediated Bcl-xL pathway.

View Article: PubMed Central - PubMed

Affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea; School of Marine Biomedical Sciences, Jeju National University, Jeju 690-756, Republic of Korea.

ABSTRACT
The anticancer effects of trans-1,3-diphenyl-2,3-epoxypropan-1-one (DPEP), a chalcone derivative, were investigated in human leukemia HL-60 cells. Treatment of HL-60 cells with various concentration of DPEP resulted in a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, and increased sub-G1 DNA content. We demonstrated that DPEP elevates reactive oxygen species (ROS) levels in HL-60 cells, and that the ROS scavenger N-acetylcysteine (NAC) could block DPEP-induced ROS generation and apoptosis. Western blot analysis revealed that DPEP inhibits Bcl-xL expression, leading to caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, thereby inducing apoptosis. However, NAC pre-treatment significantly inhibited the activation of caspase-3 and PARP cleavage and reduced Bcl-xL levels. These findings provide the first evidence that DPEP may inhibit the growth of HL-60 cells and induce apoptosis through a ROS-mediated Bcl-xL pathway.

No MeSH data available.


Related in: MedlinePlus