| 摘要: | 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的。本篇主要是研究PCA在TPA刺激下誘導上皮腫溜促進作用中分子作用的機制。
CD-1老鼠局部塗抹5nmol TPA，一天2次連續塗抹5天。利用組織化學H-E染色法在顯微鏡下觀察，結果發現老鼠背部上皮有增生。另外免疫組織化學染色不分析，結果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和 PKC。比起未塗抹的老鼠，各別有：2.39-,1.19-,2.34-,2.26-,2.47-,和2.45倍的增加。PCA的預先塗抹不擔抑制了TPA引起的增生，而且脂質過氧化現像也明顯的減少。TPA刺激引起c-Fos, MEK1,ERK1,ERK2和PKC蛋白的表現，受到５□ mol PCA的抑制。抑制百分比各別是：25,33,16,49,和16%。高劑量20□mol PCA 顯示更明顯的抑制，各別是68,6664,65和68％的抑制。另外，我們運用西方墨點吸漬法測定，預先處理5□mol PCA 會引起c-Fos, c-Jun, c-Myc,phosphotyrosine, Raf,MEK1,ERK1,ERK2和PKC蛋白表現受到抑制。各別是：1.25-,1.1-,2.75-.0.89-,17-,106-.1.91-,12.07-和0.98-。高劑量20□mol1 PCA更明顯的抑制，各別是0-,0.23-,0.35-,0-,21-,1.26-,5.69-和0.19-的抑制。這個數據和我們先前的研究顯示阻斷TPA引起訊息傳遞蛋白的表現，抑制TPA 引起的腫瘤促進作用上扮演重要的角色。
Hibiscus protocatechuic acid (PCA), a simple phenolic compound, isolated from Hibiscus sabdariffa L. was studied for its molecular mechanisms on 12-0-tetradecanoy 1phorbol 13-acetate (TPA)-induced promotion of skin tumors.
Topical application of 5 nmol 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 singaling 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,ERK2 and PKC were also significantly inhibited by PCA (5□mol) to the extent of 25,33,16,49, and 16% respectively. Higher dose of PCA (20□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.
These data and our previous results indicated that the TPA-induced enhancement of the expression of mitogenic signaling proteins plays an important role in the suppression of TPA-induced tumor promotions. |
