School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei 10630, Taiwan.
Mar Drugs. 2020 Jul 2;18(7):348. doi: 10.3390/md18070348.
Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells.
We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3',5,5'-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells.
Heteronemin inhibited not only expression of proliferative genes and () but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased expression in SCC-25 cells. Tetrac suppressed expression of but not expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent.
Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited expression. Moreover, tetrac suppressed expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.
异海松宁是一种海洋甾体型天然产物，具有抑制癌细胞增殖的作用。此外，异海松宁已被证明能抑制基因的表达。我们实验室已经证明，甲状腺激素脱氨酶类似物四碘甲状腺原氨酸（tetrac）能激活并诱导结直肠癌细胞增殖。然而，这种药物机制在口腔癌细胞中仍有待研究。
我们通过细胞计数试剂盒-8 和流式细胞术来研究细胞增殖抑制作用。通过 Western blot 分析来检测信号转导通路。采用定量 PCR 来评估异海松宁、3,3',5,5'-四碘甲状腺原氨酸（tetrac）或它们联合处理对口腔癌细胞中基因表达的调控作用。
异海松宁不仅抑制了增殖基因和的表达，而且还抑制了 OEC-M1 和 SCC-25 细胞的增殖。值得注意的是，异海松宁增加了 SCC-25 细胞中的表达。tetrac 抑制了两种癌细胞系中基因的表达，但不抑制基因的表达。此外，tetrac 和异海松宁的协同作用抑制了 ERK1/2 的激活，并且异海松宁也阻断了 STAT3 信号通路。联合治疗虽然抑制了两种癌细胞系中的表达，但增加了 p53 蛋白和 p53 激活的积累。联合治疗比单一药物更能协同诱导细胞增殖抑制。
异海松宁和 tetrac 均能抑制 ERK1/2 的激活和增加 p53 的磷酸化。它们还抑制了基因的表达。此外，tetrac 与异海松宁联合抑制表达，进一步增强了口腔癌细胞的增殖抑制和抗转移作用。
