| Abstract: | 原兒茶酸(Protocatechuic acid,PCA)是一簡單多酚類化合物,經由乾燥的洛神花萃取而來。CD-1老鼠局部塗抹5nmol TPA,一天塗抹2次,連續塗抹5天後取上皮組織以H.E. stain在顯微鏡下觀察發現老鼠背部上皮有增生的現象。此外另以免疫組織化學染色法分析上皮組織發現上皮細胞層脂質過氧化及訊息傳遞蛋白增加,包括c-Fos,Phosphotyrosine,MEK1,ERK1,ERK2及PKC。比起未塗抹者分別增加2.39,1.19,2.34,2.26,2.47及2.45倍。而PCA的預先塗抹不但抑制了TPA引起的增生,而且脂質過氧化現象也明顯的減少。TPA刺激引起c-Fos,MEK1,ERK1,ERK2及PKC蛋白的表現,受到5.mu.mol PCA的抑制,抑制百分比分別是25,33,16,49和16%,而提高劑量至20.mu.mol則顯示更明顯的抑制,分別為68,66,64,65和68%。此外以西方墨點吸漬法測定蛋白之表現,結果發現預先處理5.mu.mol PCA會引起c-Fos,c-Jun,c-Myc, Phosphotyrosine,c-Raf,MEK1,ERK1,ERK2及PKC蛋白的表現受到抑制,其抑制百分比分別為74%,4%,24%,32%,62%,55%,5%,-16%,30%。而高劑量20.mu.mol PCA則有更明顯的抑制,其抑制百分比分別為96%,71%,47%,73%,91%, 91%,27%,42%,83%。綜合這些結果及先前的研究顯示阻斷TPA引起訊息傳遞蛋白的表現,是PCA抑制TPA引起腫瘤促進作用的可能機轉。
Hibiscus protocatechuic acid (PCA), a phenolic acid isolated from Hibiscus sabdariffa L., was a chemopreventive agent. In our earlier study shown that PCA has a inhibitory effect on the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced skin tumorgenesis. Topical application of 5nmol TPA to the dorsal surface of CD-1 mice twice daily for 5 days caused epidermal hyperplasia, lipid peroxidation and the enhancement of the protein levels of the signaling proteins, such as c-Fos, MEK, ERK1, ERK2 and PKC were 2.39-, 2.34-, 2.26-, 2.47- and 2.45-fold as compared to control on TPA-treated mice epidermis. Topical application of PCA briefly prior to the application of TPA not only inhibited the TPA-induced hyperplasia but also lipid peroxidation was markedly reduced. The TPA-induced expression of c-Fos, MEK1, ERK1, ERK1 and PKC were also significantly inhibited by PCA (5.mu.mol) to the extent of 25, 33, 16, 49 and 16% respectively. Higher dose of PCA (20.mu.mol) showed even more marked inhibition on the TPA-induced expressions of these proteins described above, by 68, 66, 64, 65 and 68%, respectively, in mice epidermis. In the other side, Western blotting was used to determine the inhibitory effect of signaling protein on PCA-pretreated mice. The results also showed that PCA could inhibit the expression of TPA-induced signaling protein. These data and our previous results indicated that the TPA-induced enhancement of the expression role in suppression of TPA-induced tumor promotions. |
