114E-1


Induction of apoptosis by hydroxydibenzoylmethane through coordinative modulation of cyclin D3, Bcl-XL, and Bax, release of cytochrome c and sequential activation of caspases in human colorectal carcinoma cells

M.-H. PAN and M.-C. Huang. Marine Food Science, National Kaohsiung Institution of Marine Technology, 142, Hai-Chuan Rd. Nan-Tzu, Kaohsiung, Taiwan, Republic of China, Kaohsiung, 811, Taiwan

DBM (dibenzoylmethane) is a minor constituent of licorice that has anti-mutagenic activity. However, its other biological activities are not well-known. The structurally related b-diketone, such as DBM, hydroxydibenzoylmethane (HDB), hydroxymethyldibenzoylmethane (HMDB), were able to induce apoptosis in colorectal carcinoma COLO 205 cells. Thus, the effect of structurally related b-diketone 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 downregulation of Bcl-XL, 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 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.

Session 114E, Nutraceuticals & Functional Foods: Bioactivity measurement and mechanism
8:30 AM - 12:00 PM, Friday AM Room Hall N-1

2004 IFT Annual Meeting, July 12-16 - Las Vegas, NV