Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells

• Published in: Molecular and cellular biochemistry Vol. 310; no. 1-2; pp. 43 - 48
• Main Authors: Jin, Un-Ho, Song, Kwon-Ho, Motomura, Muneo, Suzuki, Ikukatsu, Gu, Yeun-Hwa, Kang, Yun-Jeong, Moon, Tae-Chul, Kim, Cheorl-Ho
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.03.2008; Springer US; Springer Nature B.V
• Subjects: Acids; Apoptosis; Apoptosis - drug effects; Biochemistry; Biological properties; Biomedical and Life Sciences; Caffeic Acids - pharmacology; Cardiology; Caspase 3 - metabolism; Cell Line, Tumor; Cells; Chromatin - metabolism; Cytochromes c - metabolism; DNA Fragmentation - drug effects; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - pathology; Eukaryotic Initiation Factor-2 - metabolism; fas Receptor - metabolism; Humans; Leukemia; Leukemia, Myeloid - pathology; Life Sciences; Medical Biochemistry; Mitochondria; Mitochondria - drug effects; Mitochondria - enzymology; Mitochondria - metabolism; Oncology; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Poly(ADP-ribose) Polymerases - metabolism; Propolis; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, Death Domain - metabolism; Studies; Transcription Factor CHOP - metabolism; U937 Cells; Mitochondria; Leukemia cells; CAPE; Apoptosis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-007-9663-7

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 μg/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-eIF2α 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.