Study the mechanism of Dibenzoylmethane analogues on the skin chemoprevention

• Main Authors: Yi-Hong Sin, 辛宜鴻
• Other Authors: Min-Hsiung Pan
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/36759376370957149568

碩士 === 國立高雄海洋科技大學 === 水產食品科學研究所 === 93 === Part I: Induction of apoptosis by HMDB in A431 cells We have previously shown that hydroxymethlydibenzoylmethane (HMDB) blocks proliferation and induces apoptosis in human colorectal carcinoma cells, but the mechanism of this effect has not been fully elucidated. We report that HMDB, -diketone, induces growth inhibition of human cancer cells and apoptosis of A431 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in and early stages of HMDB-induced apoptosis preceding cytochrome c release, caspase activation, and DNA fragmentation. Upregulation of Bad, p21 and downregulation of Bcl-2, Bcl-XL, Bid, p53, and fatty acid synthase (FAS), and cleavage of Bax were found in HMDB-treated A431 cells. Glutathione (GSH) and N-acetylcysteine (NAC), an antioxidant, suppresse HMDB-induced apoptosis. HMDB markedly enhanced growth inhibition and DNA damage-inducible gene 153 (DADD153) mRNA and protein expression in a time- and concentration-dependent manner. NAC prevented up-regulation of GADD153 mRNA expression caused by HMDB. These findings suggest that HMDB creates an oxidative cellular environment that induces DNA damage and GADD153 gene activation, which in turn helps trigger apoptosis in A431 cells. Part II: Inhibit two-stage carcinogenesis of mice skin by DBM analogues. Dibenzoylmethane is the micro-element in the licorice root, there are documents that point out that DBM has obviously suppressed formation of tumors. This research uses DBM and its analogues to evaluate two stage carcinogenesis in mouse model, and the suppression of the peracute inflammation of ear of mice. The result shows that suppresses formation of tumors on mouse's back, and 10 mole HMDB can reduce tumors incidence of 45% , and amount of tumors is less than DBM. The inflammation by TPA mediated inflammation will enhance two stage carcinogenesis of skin cancer. Therefore, we study the TPA-induced inflammation in mice. The result indicates that markedly suppress the expression of COX-2 and iNOS proteins. Taken together, we suggest that DBM suppresses the DMBA-mediated initiation stage, and HDB suppresses the TPA-mediated promotion stage; HMDB suppresses the function of initiate- and promote-stage in mice.