| Summary: | 博士 === 國立陽明大學 === 遺傳學研究所 === 88 === Terminalia catappa L. is a popular folk medicine for preventing hepatoma and treating hepatitis in Taiwan. In the present study, the protective effects on bleomycin-induced genotoxicity and against Ras-induced cellular transformation by T. catappa leaf water extract (TCE) and its major tannin component, punicalagin were examined.
In order to test the protective effect of TCE against gene mutations, three kinds of mutagens, alkylating agent ethyl methanesulfonate (EMS), free radical generator bleomycin and polyaromatic hydrocarbon 3-methylcholanthrene (3MCA), were used to induce hgprt gene mutation. Pre-treatments with lower doses of TCE could significantly prevent bleomycin-induced hgprt gene mutations and partially prevent EMS-induced mutations, while there is no effect on 3MCA-induced gene mutations. In addition, TCE could prevent bleomycin-induced DNA strand breaks significantly. Punicalagin also showed the preventive effects against bleomycin-induced genotoxicity. It was thought that bleomycin-induced DNA damage is mainly through reactive oxygen species (ROS) mechanism. TCE and punicalagin could suppress the generation of bleomycin-induced intracellular free radicals, which might attribute to their superoxides and hydrogen peroxides scavenging activities.
To evaluate the effect of TCE against cellular transformation, ras-transformed NIH3T3 cells were used as a malignant tumor cell system. It was demonstrated that TCE could suppress ras-transformed NIH3T3 cell growth and that was more sensitive than non-transformed NIH3T3 cells. Moreover, TCE could inhibit the anchorage-independent growth of ras-transformed NIH3T3 cell. Similarly, punicalagin also showed the suppressive effect against ras-transformed NIH3T3 cell. In addition, TCE and punicalagin could decrease the superoxide level of ras-transformed NIH3T3 cell. The modulations of the redox status by TCE and punicalagin were possibly important for inhibiting cell growth and anchorage-independent growth in ras-transformed NIH3T3 cell. Moreover, the treatment with punicalagin could inhibit the phosphorylation of JNK-1 and p38, c-Jun protein content and AP-1 binding activity. It was known that JNK-1, c-Jun and AP-1 can be regulated by ROS and that is essential for Ras transforming activity. Therefore, the modulation of these proteins may correlate with the reduction of O2- level and were possibly contribute to the suppressive effects of punicalagin against Ras-induced cellular transformation.
In summary, the present study demonstrated that TCE and punicalagin could prevent bleomycin-induced genotoxicity, which could be, at least in part, due to their antioxidative potentials. Furthermore, the antioxidative potentials of TCE and punicalagin possibly affect JNK, p38, c-Jun and AP-1 of ras-transformed NIH3T3 cell, and may result in the suppression of cell growth and anchorage-independent growth.
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