Kuo M L, Yang N C
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Biochem Biophys Res Commun. 1995 Jul 26;212(3):767-75. doi: 10.1006/bbrc.1995.2035.
Apigenin, a plant flavonoid, induced the reversion of transformed phenotypes of v-H-ras-transformed NIH 3T3 cells at a quite low concentration of 12.5 microM. In the present study, we have examined the components of this Ras-mediated signaling transduction to determine whether they were involved in the apigenin-induced reversion process. Interestingly, the consitutively activated mitogen activated protein kinase (MAPK) in the ras transformant was inhibited significantly and rapidly by 25 microM apigenin within 30 min, and this reduction continued for more than 4 h. Corroborating these observations, expression of the downstream oncogenes c-jun and c-fos was also dramatically reduced during the first 4 h of treatment. We found that the levels of ras protein and mRNA were not affected by 24 h of treatment with apigenin. These findings indicate that apigenin-induced reversion of v-H-ras-transformed NIH 3T3 cells may occur by inhibiting MAPK activity and its downstream oncogenes rather than by affecting the expression of the ras gene.
芹菜素是一种植物类黄酮，在浓度低至12.5微摩尔时就能诱导v-H-ras转化的NIH 3T3细胞的转化表型发生逆转。在本研究中，我们检测了这种Ras介导的信号转导的组成部分，以确定它们是否参与芹菜素诱导的逆转过程。有趣的是，在ras转化体中持续激活的丝裂原活化蛋白激酶（MAPK）在30分钟内被25微摩尔芹菜素显著且迅速地抑制，并且这种降低持续超过4小时。证实这些观察结果的是，在处理的前4小时内，下游癌基因c-jun和c-fos的表达也显著降低。我们发现，用芹菜素处理24小时后，ras蛋白和mRNA的水平不受影响。这些发现表明，芹菜素诱导的v-H-ras转化的NIH 3T3细胞的逆转可能是通过抑制MAPK活性及其下游癌基因，而不是通过影响ras基因的表达来实现的。
