Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Korea.
Oncol Res. 2011;19(5):237-43. doi: 10.3727/096504011x12970940207922.
We determined whether indole-3-carbinol (I3C) could affect DU145 human prostate carcinoma cell migration to prevent the development and progression of prostate cancer. Although previous studies have shown anticancer properties of I3C in various cancer cell lines, it has not been determined how I3C regulates epidermal growth factor (EGF)-induced migration and related signaling pathways. DU145 cells were treated with I3C (100 microM) in the absence or presence of EGF (10 ng/ml). Our results showed that I3C significantly inhibited DU145 cell migration with and without EGF stimulation. It has been reported that the beta-catenin signaling pathway controls androgen receptor (AR)-mediated prostate cancer progression, which plays a key role in the metastasis of prostate cancer. Western blot analysis demonstrated that I3C led to the phosphorylation of beta-catenin and subsequent degradation of beta-catenin in the absence and presence of EGF. In contrast, I3C did not have any effect on the expression of beta-catenin mRNA. From these results, we suggest that I3C inhibits EGF (dependent or independent)-induced DU145 cell migration through beta-catenin degradation.
我们旨在研究吲哚-3-甲醇（I3C）是否能影响 DU145 人前列腺癌细胞的迁移，以预防前列腺癌的发生和发展。尽管先前的研究表明 I3C 在各种癌细胞系中具有抗癌特性，但尚未确定 I3C 如何调节表皮生长因子（EGF）诱导的迁移及其相关信号通路。我们用 100μM 的 I3C 处理 DU145 细胞，同时有无 EGF（10ng/ml）刺激。结果表明，I3C 可显著抑制 DU145 细胞的迁移，无论有无 EGF 刺激。据报道，β-连环蛋白信号通路控制着雄激素受体（AR）介导的前列腺癌进展，该通路在前列腺癌转移中起着关键作用。Western blot 分析表明，I3C 导致 β-连环蛋白的磷酸化，继而在有无 EGF 的情况下降解 β-连环蛋白。相反，I3C 对 β-连环蛋白 mRNA 的表达没有任何影响。根据这些结果，我们认为 I3C 通过降解 β-连环蛋白抑制 EGF（依赖或非依赖）诱导的 DU145 细胞迁移。
