EFFECT OF CURCUMIN ON 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED AND ULTRAVIOLET-B LIGHT-INDUCED EXPRESSION OF C-JUN AND C-FOS IN JB6 CELLS AND IN MOUSE EPIDERMIS
EFFECT OF CURCUMIN ON 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED AND ULTRAVIOLET-B LIGHT-INDUCED EXPRESSION OF C-JUN AND C-FOS IN JB6 CELLS AND IN MOUSE EPIDERMIS
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DOI：
10.1093/carcin/15.10.2363
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发表时间：
1994-10-01
期刊：
影响因子：
4.7
通讯作者：
CONNEY, AH
中科院分区：
文献类型：
--
作者：
LU, YP;CHANG, RL;CONNEY, AH
在正常增殖的JB 6细胞中观察到c-Jun蛋白（c-Jun）的表达，但在汇合的细胞中没有。将细胞培养液中的血清浓度从5%降低到2%，使JB 6细胞进入静止的非增殖状态，并下调c-Jun的表达，用12-O-十四烷酰佛波醇-13-乙酸酯（TPA）（10 ng/ml）处理静止的JB 6细胞24 h，显著刺激c-Jun的形成，并引起形态学改变。用TPA处理JB 6细胞48小时导致具有混合细胞群的转化灶。虽然这些病灶中的一些细胞表达高水平的c-Jun，但许多其他细胞没有。TPA（10 ng/ml）处理JB 6细胞24 h后，c-Jun表达增加，细胞形态学改变被姜黄素（10 nmol/ml）抑制。用2.5、5或10 nmol/ml姜黄素处理JB 6细胞，分别抑制TPA诱导的在软琼脂中生长的非贴壁依赖性集落的形成31%、43%和77%。虽然在2.5 mmol姜黄素/ml时未观察到细胞增殖的抑制，但较高浓度确实抑制了细胞增殖。CD-1小鼠背部每天一次局部应用5 mmol TPA，持续5天，引起表皮增生，表皮基底上层和真皮肌肉层中的c-Jun水平增加。这种处理也增加了c-Fos蛋白（c-Fos）在肌肉层中的表达，但在表皮的基底层或基底上层中c-Fos的表达很少或没有增加。局部应用10 μ mol姜黄素与5 nmol TPA一起，每天一次，持续5天，强烈抑制TPA诱导的表皮增生和c-Jun和c-Fos表达。单次向SKH-1小鼠背部施加180 mJ/cm 2的紫外线B光（UVB）可引起表皮增生，并在真皮的肌肉层和表皮的基底上层表达c-Fos和c-Jun。在UVB暴露后6天观察到最大效应。应用10 μ mol姜黄素的小鼠皮肤，每天两次，5天后立即UVB曝光只有一个小的/可变的抑制作用UVB诱导的增加c-Fos和c-Jun的表达和表皮增生。这些数据表明，诱导增生和c-Jun和c-Fos在小鼠皮肤中的表达TPA和UVB可能涉及不同的途径，抑制TPA诱导的皮肤肿瘤发生姜黄素可能与抑制TPA诱导的c-Jun和c-Fos的表达增加。
Expression of c-jun protein (c-Jun) was observed in normally proliferating JB6 cells but not in confluent cells. Reduction of the serum concentration from 5% to 2% in the cell culture medium caused JB6 cells to enter a quiescent non-proliferating state and down-regulated the expression of c-Jun. Treatment of quiescent JB6 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 ng/ml) for 24 h markedly stimulated the formation of c-Jun and caused morphological changes. Treatment of JB6 cells with TPA for 48 h resulted in transformed foci with mixed cell populations. Although some cells in these foci expressed high levels of c-Jun, many other cells did not. The increased expression of c-Jun and morphological changes observed at 24 h after treatment of JB6 cells with TPA (10 ng/ml) was inhibited by curcumin (10 nmol/ml). Treatment of JB6 cells with 2.5, 5 or 10 nmol curcunmin/ml inhibited the formation of TPA-induced anchorage-independent colonies that grow in soft agar by 31%, 43% and 77%, respectively. Although inhibition of cell proliferation was not observed with 2.5 mmol curcumin/ml, higher concentrations did inhibit cell proliferation. Topical application of 5 mnol TPA to the backs of CD-1 mice once a day for 5 days caused epidermal hyperplasia and the levels of c-Jun were increased in the suprabasal layer of the epidermis and in the muscle layer of the dermis. This treatment also increased c-fos protein (c-Fos) expression in the muscle layer, but there was little or no increase in the expression of c-Fos in the basal or suprabasal layer of the epidermis. Topical application of 10 mu mol curcumin together with 5 nmol TPA once a day for 5 days strongly inhibited TPA-induced epidermal hyperplasia and c-Jun and c-Fos expression. A single application of 180 mJ/cm(2) of ultraviolet B light (UVB) to the backs of SKH-1 mice caused epidermal hyperplasia and expression of c-Fos and c-Jun in the muscle layer of the dermis and of c-Fos in the suprabasal layer of the epidermis. Maximum effects were observed at 6 days after UVB exposure. Application of 10 mu mol curcumin to mouse skin twice a day for 5 days immediately after UVB exposure had only a small/variable inhibitory effect on UVB-induced increases in the expression of c-Fos and c-Jun and on epidermal hyperplasia. These data suggest that induction of hyperplasia and c-Jun and c-Fos expression in mouse skin by TPA and UVB may involve different pathways and that inhibition of TPA-induced skin tumorigenesis by curcumin may be associated with inhibition of TPA-induced increases in the expression of c-Jun and c-Fos.