Department of Cardiothoracic Surgery, Qingyuan People's Hospital (The Sixth Affiliated Hospital of Guangzhou Medical University), Qingyuan, Guangdong, China (mainland).
Med Sci Monit. 2019 Apr 21;25:2935-2942. doi: 10.12659/MSM.914348.
BACKGROUND Thyroid cancer causes considerable mortality and morbidity across the globe. Owing to the unavailability of biomarkers and the adverse effects of existing drugs, there is an urgent need to develop efficient chemotherapy for the treatment of thyroid cancers. Plants have served as exceptional source of drugs for the treatment of lethal diseases. The purpose of this study was to evaluate the anticancer effects of ferruginol against thyroid cancer cells. MATERIAL AND METHODS We monitored the cell proliferation rate using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and annexin V/propidium iodide (PI) staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were examined by fluorescence microscopy. Protein expressed was examined by western blotting. RESULTS We found that ferruginol exerted potent antiproliferative action against thyroid cancer cells, and an IC₅₀ of 12 µM was observed for ferruginol against the MDA-T32 cell line. The toxic effects of ferruginol were less pronounced against normal cells. The anticancer effects of ferruginol were likely due to the induction of apoptosis which was also associated with upregulation of Bax and downregulation of Bcl-2. Ferruginol also caused ROS mediated alterations in the MMP of MDA-T32 cells. In MDA-T32 cells, ferruginol might also block the MAPK and PI3K/AKT signaling pathway, which is believed to be an important therapeutic target of anticancer drugs. CONCLUSIONS In conclusion, in view of the results of this study, it might be suggested that ferruginol might serve as an essential lead molecule for the treatment of thyroid cancer provided further in-depth studies especially studying ferruginol toxicological as well as in vivo studies are needed.
甲状腺癌在全球范围内导致相当大的死亡率和发病率。由于缺乏生物标志物和现有药物的不良反应，因此迫切需要开发有效的化疗药物来治疗甲状腺癌。植物一直是治疗致命疾病的药物的重要来源。本研究的目的是评估二氢水杨梅素对甲状腺癌细胞的抗癌作用。
我们使用 3-(4,5-二甲基噻唑-2-Yl)-2,5-二苯基四氮唑溴盐（MTT）测定法监测细胞增殖率。使用 4'，6-二脒基-2-苯基吲哚（DAPI）、吖啶橙/溴化乙锭（AO/EB）和 Annexin V/碘化丙啶（PI）染色检测细胞凋亡。通过荧光显微镜检查活性氧（ROS）和线粒体膜电位（MMP）水平。通过 Western 印迹检查蛋白质表达。
我们发现二氢水杨梅素对甲状腺癌细胞具有很强的增殖抑制作用，对 MDA-T32 细胞系的 IC₅₀为 12 µM。二氢水杨梅素对正常细胞的毒性作用不明显。二氢水杨梅素的抗癌作用可能是由于诱导细胞凋亡所致，这也与 Bax 的上调和 Bcl-2 的下调有关。二氢水杨梅素还导致 MDA-T32 细胞中 ROS 介导的 MMP 改变。在 MDA-T32 细胞中，二氢水杨梅素可能还会阻断 MAPK 和 PI3K/AKT 信号通路，这被认为是抗癌药物的重要治疗靶点。
总之，鉴于本研究的结果，我们可以建议二氢水杨梅素可能成为治疗甲状腺癌的重要先导分子，前提是需要进行进一步的深入研究，特别是需要研究二氢水杨梅素的毒理学和体内研究。
