Cho Seok-Cheol, Choi Bu Young
Department of Food Science & Engineering, Seowon University, Cheongju 361-742, Republic of Korea.
Department of Pharmaceutical Science & Engineering, Seowon University, Cheongju 361-742, Republic of Korea.
Biomol Ther (Seoul). 2015 Sep;23(5):428-33. doi: 10.4062/biomolther.2015.102. Epub 2015 Sep 1.
Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-κB signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-α (TNF-α)-induced NF-κB reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-κB activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.
乙酰紫草素是一种天然萘醌衍生物化合物,已被用于治疗炎症和癌症。在本研究中,我们研究了乙酰紫草素是否能调节核因子κB(NF-κB)信号通路,从而抑制肿瘤发生。我们观察到乙酰紫草素显著降低了几种癌细胞系的增殖,包括人胰腺PANC-1癌细胞。此外,乙酰紫草素抑制佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)或肿瘤坏死因子-α(TNF-α)诱导的NF-κB报告基因活性。蛋白质组细胞因子阵列和实时逆转录聚合酶链反应(RT-PCR)结果表明,乙酰紫草素对PMA诱导的细胞因子产生的抑制作用是在转录水平介导的,并且与NF-κB活性和基质金属蛋白酶的抑制有关。最后,我们观察到乙酰紫草素处理显著抑制了PANC-1细胞的非锚定依赖性生长。总之,我们的结果表明,乙酰紫草素有望成为未来治疗胰腺癌的一种有前景的治疗药物。