Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells.
Treatment of U937 cells with mono(2-ethylhexyl)phthalate (MEHP) for 20 h led to a dose-dependent loss of cell viability, assessed by propidium iodide (PI) staining with fluorescent activated cell sorting (FACS) analysis. The cytotoxic behavior of MEHP is attributed to the induction of apoptosis. MEHP induced activation of caspase-3, internucleosomal DNA fragmentation and the morphological features of nuclear apoptosis. Analysis with LightCycler quantitative RT-PCR demonstrated the decrease of bcl-2 and increase of bax mRNA levels. Peroxisome proliferator-activated receptor (PPAR) gamma antagonists, bisphenol A diglycidyl ether (BADGE) and GW9662, significantly inhibited the MEHP-induced caspase-3 activity and apoptotic nuclear morphological changes. Furthermore, a PPARgamma ligand, rosiglitazone synergized the MEHP-induced caspase-3 activity. These results suggest that MEHP can induce apoptosis in U937 cells through modulation of the balance of bcl-2/bax in part by PPARgamma activation.
Yokoyama
Yoshiko
Y
Division of Molecular Epidemiology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Okubo
Tomoko
T
Kano
Itsu
I
Sato
Shigeaki
S
Kano
Kazutaka
K
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000494:pharmacology; D004249:DNA Damage; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology; D020298:U937 Cells; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D004051:Diethylhexyl Phthalate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C016599:mono-(2-ethylhexyl)phthalate