Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan.
Mar Drugs. 2018 Dec 6;16(12):489. doi: 10.3390/md16120489.
A marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against cholangiocarcinoma HuccT1 and SSP-25 cells. In vitro, heteronemin altered the abilities of cell adhesion and cell migration in HuccT1 and SSP-25 cell lines. It repressed messenger ribonucleic acid (mRNA) expression levels of transforming growth factor (TGF)-β, mothers against decapentaplegic homolog (SMAD) and Myc, whose protein products play important roles in regulating cell growth, angiogenesis, and metastasis. In addition, heteronemin altered several signaling pathways. The results indicate that heteronemin was able to modulate cell adhesion, the expression of extracellular matrix (ECM) receptors, the TGF-β pathway, cell motility, the membrane integration, metastasis response, matrix metalloproteinase (MMP) remodeling, the regulation of metabolism, sprouting angiogenesis, transcription factors, and vasculogenesis in cholangiocarcinoma cell lines. The results also suggest that it activated multiple signal transduction pathways to induce an anti-proliferation effect and anti-metastasis in cholangiocarcinoma. In conclusion, heteronemin may be used as a potential medicine for anticancer therapy.
一种海洋倍半萜类天然产物，异海松脑，保留抗癌作用。在本研究中，我们研究了异海松脑在胆管癌细胞中的抗肿瘤机制，并进一步探讨了其分子靶点。最初，异海松脑对胆管癌细胞 HuccT1 和 SSP-25 表现出很强的细胞毒性作用。在体外，异海松脑改变了 HuccT1 和 SSP-25 细胞系中细胞黏附和细胞迁移的能力。它抑制了转化生长因子（TGF）-β、母亲对抗颅足畸形同源物（SMAD）和 Myc 的信使核糖核酸（mRNA）表达水平，其蛋白产物在调节细胞生长、血管生成和转移中发挥重要作用。此外，异海松脑改变了几种信号通路。结果表明，异海松脑能够调节细胞黏附、细胞外基质（ECM）受体的表达、TGF-β 途径、细胞迁移、膜整合、转移反应、基质金属蛋白酶（MMP）重塑、代谢调节、发芽血管生成、转录因子和胆管癌细胞中的血管生成。结果还表明，它激活了多种信号转导途径，在胆管癌细胞中诱导抗增殖作用和抗转移作用。总之，异海松脑可能被用作抗癌治疗的潜在药物。
