Flavone initiates a hierarchical activation of the caspase-cascade in colon cancer cells.
There is emerging evidence that dietary factors can prevent cancer by affecting the process of carcinogenesis. Flavonoids present in vegetarian food possess antioxidant activities, have scavenging effects on activated carcinogens and mutagens, affect cell cycle progression and alter gene and protein expression. We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells. Flavone induces the activation of caspases 2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase 10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
Erhart
L M
LM
Clinical Research Unit for Gastrointestinal Endocrinology, University of Marburg, 35033 Marburg, Germany.
Lankat-Buttgereit
B
B
Schmidt
H
H
Wenzel
U
U
Daniel
H
H
Göke
R
R
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D005420:Flavoproteins / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism
C494829:AIFM1 protein, human; D000590:Amino Acid Chloromethyl Ketones; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D005420:Flavoproteins; D008565:Membrane Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases; C043562:flavone