Nutrition Research and Practice

  • 제8권2호
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  • Pages.132-137
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  • 2014
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  • 1976-1457(pISSN)
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  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
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Induction of apoptosis by a hexane extract of aged black garlic in the human leukemic U937 cells

  • Park, Cheol (Department of Molecular Biology, College of Natural Sciences, Dongeui University) ;
  • Park, Sejin (Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Pusan National University) ;
  • Chung, Yoon Ho (Duksan B&F Co. LTD.) ;
  • Kim, Gi-Young (Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University) ;
  • Choi, Young Whan (Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Pusan National University) ;
  • Kim, Byung Woo (Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University)
  • 투고 : 2013.07.22
  • 심사 : 2013.12.17
  • 발행 : 2014.04.01
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초록

BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid, and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG-treated cells, confirming that HEABG-induced apoptosis is mediated through activation of caspase cascade. CONCLUSIONS: Based on the overall results, we suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent apoptosis through both intrinsic and extrinsic pathways, implying its potential therapeutic value in the treatment of leukemia.

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참고문헌

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