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Triggering of dendritic cell apoptosis by xanthohumol
Author(s) -
Xuan Nguyen Thi,
Shumilina Ekaterina,
Gulbins Erich,
Gu Shuchen,
Götz Friedrich,
Lang Florian
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900324
Subject(s) - xanthohumol , apoptosis , chemistry , microbiology and biotechnology , dna fragmentation , ceramide , programmed cell death , biochemistry , biology , ecology , key (lock)
Xanthohumol, a flavonoid from beer with anticancer activity is known to trigger apoptosis in a variety of tumor cells. Xanthohumol further has anti‐inflammatory activity. However, little is known about the effect of xanthohumol on survival and function of immune cells. The present study thus addressed the effect of xanthohumol on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. To this end, mouse bone marrow‐derived DCs were treated with xanthohumol with subsequent assessment of enzymatic activity of acid sphingomyelinase (Asm), ceramide formation determined with anti‐ceramide antibodies in FACS and immunohistochemical analysis, caspase activity utilizing FITC conjugated anti‐active caspase 8 or caspase 3 antibodies in FACS and by Western blotting, DNA fragmentation by determining the percentage of cells in the sub‐G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. As a result, xanthohumol stimulated Asm, enhanced ceramide formation, activated caspases 8 and 3, triggered DNA fragmentation and led to cell membrane scrambling, all effects virtually absent in DCs from gene targeted mice lacking functional Asm or in wild‐type cells treated with sphingomyelinase inhibitor amitriptyline. In conclusion, xanthohumol stimulated Asm leading to caspase activation and apoptosis of bone marrow‐derived DCs.