Kuo M L, Lin J K, Huang T S, Yang N C
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, R.O.C.
Cancer Lett. 1994 Nov 25;87(1):91-7. doi: 10.1016/0304-3835(94)90414-6.
Fifteen flavonoids were employed to examine their effects on the morphological changes, foci formation in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells. The data presented here demonstrated that only three specific flavonoids--apigenin, kaempferol, and genistein--exhibited the reverting effect on the transformed phenotypes of ras-3T3 cells. For example, treatment with 25 microM of these flavonoids could effectively reverse the transformed morphology of ras-3T3 cells into flatter cells with contact inhibition. Colony formation in soft agar was decreased to 0.11%, 0.15%, and 0.35% by 25 microM apigenin, kaempferol, and genistein, respectively, as compared with control (0.92%). It was also found that the proliferation of ras-3T3 cells was significantly inhibited by these compounds in a dose-dependent manner. Finally, two biochemical parameters, the content of phosphotyrosine and cAMP, were examined to see whether affected by these compounds. The results showed the phosphotyrosine content in ras-3T3 cells was dramatically decreased by apigenin and kaempferol, but that was slightly reduced by genistein. By contrast, these three flavonoids all failed to significantly alter the level of cAMP within this transformant. Based on these observations, we suggest that some specific flavonoids are capable of reverting the transforming properties of v-H-ras transformed cells. The possible mechanism of this reversion is not mediated by activating the protein kinase A or its associated pathways, but rather inhibiting tyrosine kinases, subsequently leading to the blockage of p21ras-mediated signal transduction circuitry.
采用15种黄酮类化合物研究它们对v-H-ras转化的NIH3T3细胞形态变化、软琼脂中集落形成及细胞生长的影响。此处给出的数据表明，只有三种特定的黄酮类化合物——芹菜素、山奈酚和染料木黄酮——对ras-3T3细胞的转化表型具有逆转作用。例如，用25μM这些黄酮类化合物处理可有效将ras-3T3细胞的转化形态逆转为具有接触抑制的更扁平细胞。与对照（0.92%）相比，25μM芹菜素、山奈酚和染料木黄酮分别使软琼脂中的集落形成率降至0.11%、0.15%和0.35%。还发现这些化合物以剂量依赖性方式显著抑制ras-3T3细胞的增殖。最后，检测了两个生化参数——磷酸酪氨酸和cAMP的含量，以观察是否受这些化合物影响。结果显示，芹菜素和山奈酚可使ras-3T3细胞中的磷酸酪氨酸含量显著降低，而染料木黄酮使其略有降低。相比之下，这三种黄酮类化合物均未能显著改变该转化细胞内的cAMP水平。基于这些观察结果，我们认为一些特定的黄酮类化合物能够逆转v-H-ras转化细胞的转化特性。这种逆转的可能机制不是通过激活蛋白激酶A或其相关途径介导，而是通过抑制酪氨酸激酶，随后导致p21ras介导的信号转导通路受阻。
