Lepore Saverio M, Maggisano Valentina, Lombardo Giovanni E, Maiuolo Jessica, Mollace Vincenzo, Bulotta Stefania, Russo Diego, Celano Marilena
Department of Health Sciences, "Magna Graecia" University of Catanzaro, 88100 Catanzaro, Italy.
Endocr Metab Immune Disord Drug Targets. 2019;19(1):59-66. doi: 10.2174/1871530318666180928153241.
The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects.
Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action.
MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation.
Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production.
These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.
倍半萜内酯洋蓟苦素是洋蓟叶提取物的主要成分，在许多临床前实验模型中已显示出多种生物学活性，包括抗增殖作用。
在此，我们评估了洋蓟苦素对三种人未分化甲状腺癌细胞系生长的影响，并研究其作用的分子机制。
采用MTT法评估CAL-62、8505C和SW1736细胞的活力，采用流式细胞术分析细胞周期分布。进行蛋白质免疫印迹法检测信号转导子和转录激活子3（STAT3）磷酸化水平和核因子κB（NFkB）激活情况。通过测量活性氧来分析抗氧化作用，使用丙二醛剂量来检查脂质过氧化的存在。
洋蓟苦素以剂量和时间依赖性方式显著降低CAL-62、8505C和SW1736细胞的活力，在用该化合物处理48小时后观察到半数有效浓度（EC50）约为5μM。细胞生长抑制伴随着细胞周期停滞，主要在G2/M期，并且存在相当比例的坏死细胞。在用10μM洋蓟苦素处理48小时后，还发现NFkB的核表达降低和STAT3磷酸化减少。此外，我们观察到脂质过氧化增加，而对活性氧的产生没有任何显著影响。
这些结果表明，洋蓟苦素降低未分化甲状腺癌细胞的活力并促进细胞毒性作用，这与NFkB表达降低、STAT3磷酸化减少和脂质过氧化增加有关。对这种天然化合物特性的进一步表征可能为将洋蓟苦素用作甲状腺癌治疗的佐剂开辟道路。
