Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells.
Caffeic acid phenyl ester (CAPE), a biologically active ingredient of propolis, has several interesting biological properties including antioxidant, anti-inflammatory, antiviral, immunostimulatory, anti-angiogenic, anti-invasive, anti-metastatic and carcinostatic activities. Recently, several groups have reported that CAPE is cytotoxic to tumor cells but not to normal cells. In this study, we investigated the mechanism of CAPE-induced apoptosis in human myeloid leukemia U937 cells. Treatment of U937 cells with CAPE decreased cell viability in a dose-dependent and time-dependent manner. DNA fragmentation assay revealed the typical ladder profile of oligonucleosomal fragments in CAPE-treated U937 cells. In addition, as evidenced by the nuclear DAPI staining experiment, we observed that the nuclear condensation, a typical phenotype of apoptosis, was found in U937 cells treated with 5 microg/ml of CAPE. Therefore, it was suggested that CAPE is a potent agent inducing apoptosis in U937 cells. Apoptotic action of the CAPE was accompanied by release of cytochrome C, reduction of Bcl-2 expression, increase of Bax expression, activation/cleavage of caspase-3 and activation/cleavage of PARP in U937 cells, but not by Fas protein, an initial mediator in the death signaling, or by phospho-eIF2 alpha and CHOP, crucial mediators in ER-mediated apoptosis. From the results, it was concluded that CAPE induces the mitochondria-mediated apoptosis but not death receptors- or ER-mediated apoptosis in U937 cells.
Department of Biological Sciences, Molecular and Cellular Glycobiology Unit, Sungkyunkwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
Un-Ho
UH
Jin
Kwon-Ho
KH
Song
Muneo
M
Motomura
Ikukatsu
I
Suzuki
Yeun-Hwa
YH
Gu
Yun-Jeong
YJ
Kang
Tae-Chul
TC
Moon
Cheorl-Ho
CH
Kim
D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism
D002109:Caffeic Acids; D002843:Chromatin; D015852:Eukaryotic Initiation Factor-2; C491901:FAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D019014:fas Receptor; D051742:Transcription Factor CHOP; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol