Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells
Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells
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二烯丙基三硫醚诱导未分化甲状腺癌 8505C 细胞 G2/M 细胞周期停滞和细胞凋亡
DOI：
10.1039/c9fo00646j
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Lu Rongrong
中科院分区：
文献类型：
--
作者：
Zheng Jiangxia;Cheng Xian;Xu Shichen;Zhang Li;Pan Jie;Yu Huixin;Bao Ji;ong;Lu Rongrong
甲状腺未分化癌（ATC）是最具侵袭性的甲状腺癌。目前的方法包括手术、化疗和治疗药物，为 ATC 患者带来的益处有限。二烯丙基三硫化物 (DATS) 已被证明是一种有前景的治疗多种癌症的抗癌剂。然而，其在 ATC 肿瘤发生中的作用仍不清楚。我们的结果表明，12.5、25 和 50 μM 的 DATS 处理会以时间和剂量依赖性方式降低 8505C 细胞的活力。 H2A.X 的磷酸化是一种 DNA 损伤标记，由 DATS 以剂量和时间依赖性方式诱导。此外，DATS通过ATM而不是ATR的磷酸化介导DNA损伤。 DATS 还诱导 G2/M 细胞周期停滞，随后 Cdc25C 从细胞核易位到细胞质。进一步的结果表明，Hoechst/PI 双染色、PI-Annexin V 测定和蛋白质印迹证明 DATS 诱导 8505C 细胞中线粒体凋亡。总而言之，我们的研究结果表明，DATS 通过触发 ATC 8505C 细胞中的 DNA 损伤，诱导 G2/M 细胞周期停滞和线粒体凋亡，这为 ATC 治疗提供了一种新的治疗方法。
Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer. Current approaches including surgery, chemotherapy and therapeutic drugs provide limited benefits for ATC patients. Diallyl trisulfide (DATS) has been documented as a promising anti-cancer agent for various carcinomas. However, its role in ATC tumorigenesis remained unclear. Our results showed that DATS treatment at 12.5, 25 and 50 μM decreased the viability of 8505C cells both in a time- and dose-dependent manner. The phosphorylation of H2A.X, which is a DNA damage marker, was induced by DATS both in a dose- and time-dependent manner. Moreover, DATS mediated the DNA damage through the phosphorylation of ATM but not ATR. DATS also induced G2/M cell-cycle arrest followed by the translocation of Cdc25C from the nucleus to the cytoplasm. Further results showed that DATS induced mitochondrial apoptosis in 8505C cells, evidenced by Hoechst/PI double staining, PI-Annexin V assay and western blot. Taken altogether, our findings demonstrated that DATS induced G2/M cell-cycle arrest and mitochondrial apoptosis by triggering DNA damage in ATC 8505C cells, which shed light on a novel therapeutic approach for ATC treatment.