The Applications of Cantharidin and Cantharidin Derivatives as Photo-initiated DNA Cleavage Agents

• Main Authors: Chiu-Yen, 吳秋燕
• Other Authors: Chi-Jung Su
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/07387480860185516306

碩士 === 中山醫學大學 === 應用化學系碩士班 === 97 === Previous studies indicated that cantharidin (exo-2,3-dimethy-7-oxabicyclo [ 2,2,1 ] heptane-2,3-dicarboxylic anhydride)could inhibit the proliferation of cancer cells via p53 dependent mechanism. It could also inhibit protein phosphatases 1(PP1) and protein phosphatases 2A( PP2A ). When cancer cell was treated with cantharidin, it could induce to produce oxidative stress. Oxidative stress would cause increments of single and double stand DNA damage. But the mechanism of anticancer is still not clear. Here, cantharidin and cantharidin derivatives could be served as photo-initiated DNA cleavage agents. We irradiated at λ=352 nm to see whether they have the ability to cleave the super-coiled DNA. The results displayed that the cantharidin derivatives ( 2,6-Dimethyl-4-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-10-oxa-4-aza-tricyclo[5.2.1.02,6]decane-3,5-dione ) could cause DNA scission at acidic condition upon UV irradiation. Then, we used high-resolution gel electrophoresis to analyze the cleavage patterns. The Maxma-Gilbert sequencing data were served as sequence-specific or base-specific cleavage marks. The results indicated that cantharidin derivatives ( 2,6-Dimethyl-4-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-10-oxa-4-aza-tricyclo[5.2.1.02,6]decane-3,5-dione ) have better ability of cleavage at the guanine site.