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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

(A) Chemical structure of DPEP; (B) DPEP and its effect on various cancer cells viability. Cells in wells of 96-well plates were incubated with the various concentration of DPEP for 24 h. Cell viability was determined by a MTT assay. Each value indicates that the mean ± standard error from three independent experiments. *p < 0.05 indicate significant differences from control (without sample).
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Figure 1: (A) Chemical structure of DPEP; (B) DPEP and its effect on various cancer cells viability. Cells in wells of 96-well plates were incubated with the various concentration of DPEP for 24 h. Cell viability was determined by a MTT assay. Each value indicates that the mean ± standard error from three independent experiments. *p < 0.05 indicate significant differences from control (without sample).

Mentions: DPEP (Figure 1A(Fig. 1)), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), RNase A, propidium iodide (PI), 2' 7'-dichlorodihydrofluorescein diacetate (DCFH2-DA), dimethyl sulfoxide (DMSO), N-acetylcysteine (NAC), phosphate buffered saline (PBS), RIPA buffer and Hoechst 33342 were purchased from Sigma-Aldrich (St. Louis, MO, USA). RPMI-1640 medium, Dulbecco's Modified Eagle's Medium (DMEM), fetal bovine serum (FBS), penicillin-streptomycin, and trypsin-EDTA were purchased from Gibco/BRL (Burlington, ON, Canada). Antibodies against Bax, Bcl-xL, cleaved capspase-3, PARP, and β-actin were obtained from Cell Signaling Technology (Bedford, MA, USA). All other chemicals and reagents used in these investigations were of analytical grade.


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)

(A) Chemical structure of DPEP; (B) DPEP and its effect on various cancer cells viability. Cells in wells of 96-well plates were incubated with the various concentration of DPEP for 24 h. Cell viability was determined by a MTT assay. Each value indicates that the mean ± standard error from three independent experiments. *p < 0.05 indicate significant differences from control (without sample).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: (A) Chemical structure of DPEP; (B) DPEP and its effect on various cancer cells viability. Cells in wells of 96-well plates were incubated with the various concentration of DPEP for 24 h. Cell viability was determined by a MTT assay. Each value indicates that the mean ± standard error from three independent experiments. *p < 0.05 indicate significant differences from control (without sample).
Mentions: DPEP (Figure 1A(Fig. 1)), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), RNase A, propidium iodide (PI), 2' 7'-dichlorodihydrofluorescein diacetate (DCFH2-DA), dimethyl sulfoxide (DMSO), N-acetylcysteine (NAC), phosphate buffered saline (PBS), RIPA buffer and Hoechst 33342 were purchased from Sigma-Aldrich (St. Louis, MO, USA). RPMI-1640 medium, Dulbecco's Modified Eagle's Medium (DMEM), fetal bovine serum (FBS), penicillin-streptomycin, and trypsin-EDTA were purchased from Gibco/BRL (Burlington, ON, Canada). Antibodies against Bax, Bcl-xL, cleaved capspase-3, PARP, and β-actin were obtained from Cell Signaling Technology (Bedford, MA, USA). All other chemicals and reagents used in these investigations were of analytical grade.

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