Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 21990, Korea.
Molecules. 2019 Apr 10;24(7):1414. doi: 10.3390/molecules24071414.
Hepatocellular carcinoma (HCC) is one of the most deadly genetic diseases, but surprisingly chemotherapeutic approaches against HCC are only limited to a few targets. In particular, considering the difficulty of a chemotherapeutic drug development in terms of cost and time enforces searching for surrogates to minimize effort and maximize efficiency in anti-cancer therapy. In spite of the report that approximately one thousand lichen-derived metabolites have been isolated, the knowledge about their functions and consequences in cancer development is relatively limited. Moreover, one of the major second metabolites from lichens, Atranorin has never been studied in HCC. Regarding this, we comprehensively analyze the effect of Atranorin by employing representative HCC cell lines and experimental approaches. Cell proliferation and cell cycle analysis using the compound consistently show the inhibitory effects of Atranorin. Moreover, cell death determination using Annexin-V and (Propidium Iodide) PI staining suggests that it induces cell death through necrosis. Lastly, the metastatic potential of HCC cell lines is significantly inhibited by the drug. Taken these together, we claim a novel functional finding that Atranorin comprehensively suppresses HCC tumorigenesis and metastatic potential, which could provide an important basis for anti-cancer therapeutics.
肝细胞癌 (HCC) 是最致命的遗传疾病之一，但令人惊讶的是，针对 HCC 的化疗方法仅局限于少数几个靶点。特别是，考虑到化疗药物开发在成本和时间方面的困难，需要寻找替代品，以在抗癌治疗中最小化努力并最大化效率。尽管有报道称已经分离出大约一千种地衣衍生的代谢物，但关于它们在癌症发展中的功能和后果的知识相对有限。此外，地衣的主要次级代谢物之一，阿特拉诺林从未在 HCC 中进行过研究。关于这一点，我们通过使用代表性的 HCC 细胞系和实验方法，全面分析了阿特拉诺林的作用。该化合物对细胞增殖和细胞周期分析显示出一致的抑制作用。此外，使用 Annexin-V 和（碘化丙啶）PI 染色进行细胞死亡测定表明，它通过坏死诱导细胞死亡。最后，该药物显著抑制 HCC 细胞系的转移潜力。综上所述，我们提出了一个新的功能发现，即阿特拉诺林全面抑制 HCC 肿瘤发生和转移潜力，这可为癌症治疗提供重要依据。
