Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.
Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells.
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DOI：
10.3892/mmr.2015.4053
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发表时间：
2015-10
影响因子：
3.4
通讯作者：
Pfragner R
中科院分区：
文献类型：
--
作者：
Aguiriano-Moser V;Svejda B;Li ZX;Sturm S;Stuppner H;Ingolic E;Höger H;Siegl V;Meier-Allard N;Sadjak A;Pfragner R
甲状腺髓样癌（MTC）起源于甲状腺的C细胞，对放疗或化疗不敏感。因此，手术切除整个肿瘤组织是MTC的唯一治愈性治疗。本研究的目的是研究提取物Trailliaedoxa gracilis（TG; WW Smith & Forrest），从四川省，中国，和熊果酸（UA），五环三萜存在于TG，对MTC-SK MTC细胞系的作用的潜在机制。在体外共检测了13个TG组分和UA对细胞形态、细胞数量、增殖和凋亡率的影响。逆转录-定量聚合酶链反应核因子-κB必需修饰物（NEMO）进行描绘的作用与UA治疗后的凋亡途径。在异种移植的携带MTC的严重联合免疫缺陷小鼠中检测TG和UA。TG组分表现出抗增殖作用，在正常对照细胞未受到损害的浓度下抑制肿瘤细胞中的线粒体活性。测定用TG组分和UA处理的MTC-SK细胞的凋亡率，其中在处理的MTC小鼠中没有观察到显著的肿瘤抑制，并且在处理的MTC-SK细胞中没有检测到NEMO表达的变化。caspase 8的早发性活化的观察表明，负责任的因子与NEMO，一种抗凋亡蛋白有关。然而，在MTC-SK细胞与UA处理后，NEMO的mRNA转录水平没有差异，表明该蛋白与信号转导和转录激活因子3途径无关。
Medullary thyroid carcinoma (MTC) originates from the C-cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC-SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription-quantitative polymerase chain reaction of nuclear factor-κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC-bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC-SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC-mice, and no change in the expression of NEMO was detected in the treated MTC-SK cells. The observation of early-onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti-apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC-SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway.