Premium
Xanthohumol induces apoptosis in cultured 40‐16 human colon cancer cells by activation of the death receptor‐ and mitochondrial pathway
Author(s) -
Pan Lydia,
Becker Hans,
Gerhäuser Clarissa
Publication year - 2005
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.200500065
Subject(s) - apoptosis , xanthohumol , poly adp ribose polymerase , caspase , microbiology and biotechnology , programmed cell death , biology , cell growth , bcl 2 associated x protein , cell culture , chemistry , caspase 3 , biochemistry , polymerase , enzyme , ecology , genetics , key (lock)
Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones ( Humulus lupulus L.). In this study, we investigated the cell growth inhibitory potential of XN on cultured human colon cancer cells. Cell proliferation was measured by sulforhodamine B staining. Poly(ADP‐ribose)polymerase (PARP) cleavage, activation of caspases‐3, ‐7, ‐8, and ‐9, and Bcl‐2 family protein expression were detected by Western blot analyses. XN significantly reduced proliferation of the HCT116‐derived colon cancer cell line 40‐16. Half‐maximal inhibitory concentrations decreased from 4.1 μ M after 24 h treatment to 3.6 and 2.6 μ M after 48 and 72 h incubation, respectively. Treatment with 15 μ M XN for 48 h and with 5 μ M for 72 h led to the detection of the cleaved 89 kDa fragment of 116 kDa PARP as an indication of apoptosis induction. Concomitantly, we observed activation and cleavage of the effector caspases‐3 and ‐7, induced by activation of the initiator caspases ‐8 and ‐9. Expression of antiapoptotic Bcl‐2 was downregulated when the cells were treated with XN for 48–72 h. We conclude that induction of apoptosis by downregulation of Bcl‐2 and activation of the caspase cascade may contribute to the chemopreventive or therapeutic potential of XN.