Gastric cancer and cervical cancer are two major malignant tumors that threaten human health. The novel chemotherapeutic drugs are needed urgently to treat gastric cancer and cervical cancer with high anticancer activity and metabolic stability. Previously we have reported the synthesis, characterization and identification of a novel combretastatin A-4 analog, 3-(3-methoxyphenyl)-6-(3-amino-4- methoxyphenyl) -7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazine (XSD-7). In this study, we sought to investigate its anticancer mechanisms in a human gastric cancer cell line (SGC-7901 cells) and human cervical carcinoma cell line (HeLa cells). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that XSD-7 induced cytotoxicity in SGC-7901 and HeLa cells with inhibitory concentration 50 values of 0.11 ± 0.03 and 0.12 ± 0.05 µM, respectively. Immunofluorescence studies proved that XSD-7 inhibited microtubule polymerization during cell division in SGC-7901 and HeLa cells. Then, these cells were arrested at G2/M cell cycle and subsequently progressed into apoptosis. In further study, mitochondrial membrane potential analysis and Western blot analysis demonstrated that XSD-7 treatment-induced SGC-7901 cell apoptosis via both the mitochondria-mediated pathway and the death receptor-mediated pathway. In contrast, XSD-7 induced apoptosis in HeLa cells mainly via the mitochondria-mediated pathway. Hence, our data indicate that XSD-7 exerted antiproliferative activity by disrupting microtubule dynamics, leading to cell cycle arrest, and eventually inducing cell apoptosis. XSD-7 with novel structure has the potential to be developed for therapeutic treatment of gastric cancer and cervical cancer.

中文翻译：

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3-（3-甲氧基苯基）-6-（3-氨基-4-甲氧基苯基）-7H- [1,2,4]三唑[3,4-b] [1,3,4]噻二嗪，一种新型微管蛋白抑制剂引起SGC-7901和HeLa细胞中的G2 / M细胞周期停滞和凋亡。

胃癌和宫颈癌是威胁人类健康的两个主要恶性肿瘤。迫切需要具有高抗癌活性和代谢稳定性的新型化疗药物来治疗胃癌和宫颈癌。以前我们已经报道了新型康普他汀A-4类似物3-（3-甲氧基苯基）-6-（3-氨基-4-甲氧基苯基）-7H- [1,2,4]三唑[ 3,4-b] [1,3,4]噻二嗪（XSD-7）。在这项研究中，我们试图研究其在人胃癌细胞系（SGC-7901细胞）和人宫颈癌细胞系（HeLa细胞）中的抗癌机制。3-（4,5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物测定表明XSD-7诱导SGC-7901和HeLa细胞的细胞毒性，抑制浓度50值为0.11±0.03和0.12±0.05 µM ，分别。免疫荧光研究证明XSD-7在SGC-7901和HeLa细胞的细胞分裂过程中抑制了微管聚合。然后，这些细胞在G2 / M细胞周期停滞，随后进入凋亡状态。在进一步的研究中，线粒体膜电位分析和蛋白质印迹分析表明，XSD-7处理通过线粒体介导的途径和死亡受体介导的途径诱导了SGC-7901细胞凋亡。相反，XSD-7主要通过线粒体介导的途径诱导HeLa细胞凋亡。因此，我们的数据表明XSD-7通过破坏微管动力学，导致细胞周期停滞并最终诱导细胞凋亡而发挥抗增殖活性。