Allegri Lorenzo, Rosignolo Francesca, Mio Catia, Filetti Sebastiano, Baldan Federica, Damante Giuseppe
Department of Medical Area, University of Udine, 33100, Udine, Italy.
Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
J Cancer Res Clin Oncol. 2018 Feb;144(2):285-294. doi: 10.1007/s00432-017-2555-7. Epub 2017 Dec 2.
The anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer with a high mortality rate. Since nutraceuticals may exert beneficial effects on tumor biology, here, effects of four of these compounds [resveratrol, genistein, curcumin and epigallocatechin-3-gallate (EGCG)] on ATC cell lines were investigated.
Two ATC-derived cell lines were used: SW1736 and 8505C. Cell viability and in vitro aggressiveness was tested by MTT and soft agar assays. Apoptosis was investigated by Western Blot, using an anti-cleaved-PARP antibody. mRNA and miRNA levels were quantified by real-time PCR.
All tested nutraceuticals caused in both cell lines decrease of cell viability and increase of apoptosis. In contrast, only curcumin reduced in vitro aggressiveness in both SW1736 and 8505C cell lines, while genistein and EGCG determined a reduction of colony formation only in 8505C cells. Effects on genes related to the thyroid-differentiated phenotype were also tested: resveratrol and genistein administration determined the increment of almost all tested mRNAs in both cell lines. Instead curcumin and EGCG treatments had opposite effects in the two cell lines, causing the increment of almost all the mRNAs in 8505C cells and their reduction in SW1736. Finally, effects of nutraceuticals on levels of several miRNAs, known as important in thyroid cancer progression (hsa-miR-221, hsa-miR-222, hsa-miR-21, hsa-miR-146b, hsa-miR-204), were tested. Curcumin induced a strong and significant reduction of all miR analyzed, except for has-miR-204, in both cell lines.
Altogether, our results clearly indicate the anti-cancer proprieties of curcumin, suggesting the promising use of this nutraceutical in ATC treatment. Resveratrol, genistein and EGCG have heterogeneous effects on molecular features of ATC cells.
间变性甲状腺癌（ATC）是最具侵袭性的甲状腺癌，死亡率很高。由于营养保健品可能对肿瘤生物学产生有益影响，因此本文研究了其中四种化合物[白藜芦醇、染料木黄酮、姜黄素和表没食子儿茶素-3-没食子酸酯（EGCG）]对ATC细胞系的影响。
使用两种源自ATC的细胞系：SW1736和8505C。通过MTT和软琼脂试验检测细胞活力和体外侵袭性。使用抗切割的PARP抗体通过蛋白质免疫印迹法研究细胞凋亡。通过实时PCR定量mRNA和miRNA水平。
所有测试的营养保健品均导致两种细胞系的细胞活力降低和细胞凋亡增加。相比之下，只有姜黄素在SW1736和8505C细胞系中均降低了体外侵袭性，而染料木黄酮和EGCG仅在8505C细胞中减少了集落形成。还测试了对与甲状腺分化表型相关基因的影响：给予白藜芦醇和染料木黄酮可使两种细胞系中几乎所有测试的mRNA增加。相反，姜黄素和EGCG处理在两种细胞系中具有相反的作用，导致8505C细胞中几乎所有mRNA增加，而在SW1736细胞中减少。最后，测试了营养保健品对几种在甲状腺癌进展中起重要作用的miRNA（hsa-miR-221、hsa-miR-222、hsa-miR-21、hsa-miR-146b、hsa-miR-204）水平的影响。姜黄素在两种细胞系中均导致除has-miR-204外所有分析的miR显著降低。
总之，我们的结果清楚地表明了姜黄素的抗癌特性，表明这种营养保健品在ATC治疗中具有广阔的应用前景。白藜芦醇、染料木黄酮和EGCG对ATC细胞的分子特征具有不同的影响。
