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

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Abstract

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.

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Abbreviations

AIF:

Apoptosis inducing factor

CAPE:

Caffeic acid phenyl ester

CHOP:

C/EBP homologous factor

DAPI:

4,6-Diamidino-2-phenylindol

eIF2:

Eukaryotic initiation factor 2

GAPDH:

Glyceraldehydes-3-phosphate dehydrogenase

PARP:

Poly (ADP-ribose) polymerase

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Acknowledgement

This study was in part supported by KHIDI, Ministry of Health and Welfare, Korea.

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Authors and Affiliations

  1. 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 Jin, Kwon-Ho Song, Yun-Jeong Kang & Cheorl-Ho Kim

  2. Department of Radiological Technology, Suzuka University of Medical Science, Suzuka City, Mie, Japan

    Muneo Motomura, Ikukatsu Suzuki & Yeun-Hwa Gu

  3. Faculty of Pharmacy, Yeong-Nam University, Gyeongsan, Gyeongbuk, Korea

    Tae-Chul Moon

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  1. Un-Ho Jin
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Correspondence to Cheorl-Ho Kim.

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Jin and Song contributed equally to this article.

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Jin, UH., Song, KH., Motomura, M. et al. Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells. Mol Cell Biochem 310, 43–48 (2008). https://doi.org/10.1007/s11010-007-9663-7

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  • DOI: https://doi.org/10.1007/s11010-007-9663-7

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