Department of Chemistry, Tamkang University, New Taipei, Taiwan, ROC.
Cancer Lett. 2011 Dec 1;311(1):11-9. doi: 10.1016/j.canlet.2011.06.007. Epub 2011 Jun 25.
Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol.
HER2 癌基因的过表达促进肿瘤细胞的侵袭、转移和血管生成，并与不良预后相关。厚朴酚已被报道具有抗肿瘤活性。然而，在 HER2 阳性癌细胞中，厚朴酚的作用机制尚未得到研究。因此，我们研究了厚朴酚对 HER2 过表达卵巢癌细胞的抗癌作用。厚朴酚处理导致 HER2 基因表达在转录水平上呈剂量依赖性抑制，可能部分通过抑制 NF-κB 激活。厚朴酚处理 HER2 过表达卵巢癌细胞下调了 HER2 下游的 PI3K/Akt 信号通路，并抑制了下游靶基因血管内皮生长因子（VEGF）、基质金属蛋白酶 2（MMP2）和细胞周期蛋白 D1 的表达。一致地，表皮生长因子的共同处理可以防止厚朴酚介导的 MMP2 活性抑制。迁移实验表明，厚朴酚处理显著降低了 HER2 过表达卵巢癌细胞的迁移能力。此外，厚朴酚诱导的 HER2 过表达卵巢癌细胞凋亡的特征是切割多聚（ADP-核糖）聚合酶（PARP）和激活的 caspase 3 的上调。这些发现表明，厚朴酚可能作用于 HER2 及其下游的 PI3K/Akt/mTOR 信号网络，从而抑制 HER2 介导的转化和 HER2 过表达卵巢癌的转移潜能。这些结果提供了一种新的机制来解释厚朴酚的抗癌作用。
