Molecular and Cellular Biochemistry

, Volume 310, Issue 1–2, pp 43–48 | Cite as

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

  • Un-Ho Jin
  • Kwon-Ho Song
  • Muneo Motomura
  • Ikukatsu Suzuki
  • Yeun-Hwa Gu
  • Yun-Jeong Kang
  • Tae-Chul Moon
  • Cheorl-Ho Kim
Article

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.

Keywords

CAPE Apoptosis Mitochondria Leukemia cells 

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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Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Un-Ho Jin
    • 1
  • Kwon-Ho Song
    • 1
  • Muneo Motomura
    • 2
  • Ikukatsu Suzuki
    • 2
  • Yeun-Hwa Gu
    • 2
  • Yun-Jeong Kang
    • 1
  • Tae-Chul Moon
    • 3
  • Cheorl-Ho Kim
    • 1
  1. 1.Department of Biological Sciences, Molecular and Cellular Glycobiology UnitSungkyunkwan UniversitySuwon CityKorea
  2. 2.Department of Radiological TechnologySuzuka University of Medical ScienceSuzuka CityJapan
  3. 3.Faculty of PharmacyYeong-Nam UniversityGyeongsanKorea

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