BACKGROUND: During the process of tumorigenesis most colon cancer cells acquire resistance to apoptosis. The short chain fatty acid butyrate is well established as an antitumour agent which selectively induces apoptosis in colon cancer cells but not in normal intestinal epithelial cells. AIMS: To analyse the signalling pathway of butyrate induced apoptosis. METHODS: Using Caco-2 cells we focused on the bcl family of proteins, mitochondrial pathway, and caspase signalling cascade involved in butyrate induced apoptosis. Techniques employed included western blots, immunofluorescence, as well as experiments with peptide inhibitors of specific caspases. RESULTS: Butyrate induced a clear shift of the mitochondrial bcl rheostat towards a proapoptotic constellation, as demonstrated by upregulation of proapoptotic bak accompanied by reduced antiapoptotic bcl-x(L) levels. This was associated with translocation of cytochrome-c from the mitochondria to the cytosol, resulting in activation of the caspase cascade via caspase-9. Key executioner enzymes were caspases-3 and -1. No effect of butyrate on regulatory proteins of the inhibitor of apoptosis family was observed. CONCLUSIONS: Butyrate induced Caco-2 cell apoptosis via the mitochondrial pathway. Upregulation of bak and translocation of cytochrome-c were upstream of the caspase cascade. Subsequently, this cascade was activated via the formation of an apoptosome.
BACKGROUND: During the process of tumorigenesis most colon cancer cells acquire resistance to apoptosis. The short chain fatty acidbutyrate is well established as an antitumour agent which selectively induces apoptosis in colon cancer cells but not in normal intestinal epithelial cells. AIMS: To analyse the signalling pathway of butyrate induced apoptosis. METHODS: Using Caco-2 cells we focused on the bcl family of proteins, mitochondrial pathway, and caspase signalling cascade involved in butyrate induced apoptosis. Techniques employed included western blots, immunofluorescence, as well as experiments with peptide inhibitors of specific caspases. RESULTS:Butyrate induced a clear shift of the mitochondrial bcl rheostat towards a proapoptotic constellation, as demonstrated by upregulation of proapoptotic bak accompanied by reduced antiapoptotic bcl-x(L) levels. This was associated with translocation of cytochrome-c from the mitochondria to the cytosol, resulting in activation of the caspase cascade via caspase-9. Key executioner enzymes were caspases-3 and -1. No effect of butyrate on regulatory proteins of the inhibitor of apoptosis family was observed. CONCLUSIONS:Butyrate induced Caco-2 cell apoptosis via the mitochondrial pathway. Upregulation of bak and translocation of cytochrome-c were upstream of the caspase cascade. Subsequently, this cascade was activated via the formation of an apoptosome.
Authors: I Marzo; C Brenner; N Zamzami; J M Jürgensmeier; S A Susin; H L Vieira; M C Prévost; Z Xie; S Matsuyama; J C Reed; G Kroemer Journal: Science Date: 1998-09-25 Impact factor: 47.728
Authors: S A Susin; H K Lorenzo; N Zamzami; I Marzo; B E Snow; G M Brothers; J Mangion; E Jacotot; P Costantini; M Loeffler; N Larochette; D R Goodlett; R Aebersold; D P Siderovski; J M Penninger; G Kroemer Journal: Nature Date: 1999-02-04 Impact factor: 49.962
Authors: Anderly C Chüeh; Janson W T Tse; Michael Dickinson; Paul Ioannidis; Laura Jenkins; Lars Togel; BeeShin Tan; Ian Luk; Mercedes Davalos-Salas; Rebecca Nightingale; Matthew R Thompson; Bryan R G Williams; Guillaume Lessene; Erinna F Lee; Walter D Fairlie; Amardeep S Dhillon; John M Mariadason Journal: Clin Cancer Res Date: 2017-06-13 Impact factor: 12.531
Authors: Jennifer S Waby; Haridasan Chirakkal; ChenWei Yu; Gareth J Griffiths; Roderick S P Benson; Colin D Bingle; Bernard M Corfe Journal: Mol Cancer Date: 2010-10-15 Impact factor: 27.401
Authors: Bernard M Corfe; Elizabeth A Williams; Jonathan P Bury; Stuart A Riley; Lisa J Croucher; Daphne Y L Lai; Caroline A Evans Journal: BMC Cancer Date: 2009-09-18 Impact factor: 4.430