Induction of apoptosis by hydroxydibenzoylmethane through coordinative modulation of cyclin D3, Bcl-X L , and Bax, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
51
Journal Issue
14
Pages
3977-3984
Date Issued
2003
Author(s)
Abstract
DBM (dibenzoylmethane) is a minor constituent of licorice that has antimutagenic activity. However, its other biological activities are not well-known. The structurally related £]-diketones hydroxydibenzoylmethane (HDB) and hydroxymethyldibenzoylmethane (HMDB) were able to induce apoptosis in colorectal carcinoma COLO 205 cells. Thus, the effect of structurally related £]-diketones on cell viability, DNA fragmentation, and caspase activity was assessed. The potency of these compounds on these features of apoptosis were in the order of HDB > HMDB > DBM in colorectal carcinoma COLO 205 cells. Here, we found that HDB-induced apoptotic cell death was accompanied by upregulation of cyclin D3, Bax, and p21 and down-regulation of Bcl-X L , while HDB had no effect on the levels of Bcl-2 and Bad protein. These results indicate that HDB allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 degradation. It is suggested that HDB-induced apoptosis is triggered by the release of cytochrome c into cytosol, procaspase-9 processing, activation of caspase-3 and caspase-2, degradation of PARP, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by HDB may provide a pivotal mechanism for its cancer chemopreventive action.
Subjects
Apoptosis
Caspase-2
Caspase-3
Caspase-9
Caspase-activated deoxyribonuclease
Cytochrome c
DBM
DNA fragmentation factor
HDB
HMDB
Poly-(ADP-ribose) polymerase
SDGs
Other Subjects
antimutagenic agent; caspase; caspase 2; caspase 3; cyclin D3; cytochrome c; deoxyribonuclease; diketone; enzyme inhibitor; enzyme precursor; hydroxydibenzoylmethane; hydroxymethyldibenzoylmethane; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein BAD; protein Bax; protein bcl 2; protein bcl xl; protein p21; unclassified drug; apoptosis; article; cell line; cell strain COLO 205; cell viability; chemoprophylaxis; colorectal carcinoma; controlled study; DNA degradation; DNA strand breakage; drug mechanism; drug potency; drug structure; enzyme activation; enzyme release; gene expression; Glycyrrhiza; human; human cell; protein degradation; signal transduction; Antioxidants; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Benzoates; Caspase 3; Caspases; Cell Survival; Chalcones; Colorectal Neoplasms; Cyclins; Cytochrome c Group; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Gene Expression; Humans; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Glycyrrhiza
Type
journal article