Helveticoside展示了针对结直肠癌的p53依赖性抗癌活性。,Archives of Medical Research

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Helveticoside展示了针对结直肠癌的p53依赖性抗癌活性。
Archives of Medical Research ( IF 4.7 ) Pub Date : 2020-03-06 , DOI: 10.1016/j.arcmed.2020.02.007
Na An ₁ , Ying Sun ₂ , Ligang Ma ₁ , Shengli Shi ₁ , Xiaoke Zheng ₃ , Weisheng Feng ₃ , Zhiming Shan ₄ , Yongguang Han ₁ , Le Zhao ₁ , Huiming Wu ₁

Affiliation

背景技术对天然产物及其衍生物的抗癌活性的研究代表了开发用于治疗大肠癌的安全有效的化学治疗剂的有效方法。Helveticoside是Descruinia sophia种子提取物的生物活性成分。据报道，该化合物可调节与肺癌细胞中细胞增殖和凋亡相关的基因，但其抗癌活性尚未得到充分研究。方法采用MTT法和锥虫蓝排除法评价细胞活力。流式细胞仪检测细胞凋亡。使用JC1-线粒体膜电位测定试剂盒测定线粒体膜电位。通过蛋白质印迹法测定蛋白质水平；在异种移植裸鼠模型中评估体内肿瘤生长。结果目前的研究证明了Helveticoside使用结直肠癌细胞SW480和HCT116对结直肠癌的体外抗癌活性。此外，发现凋亡的诱导介导Helveticoside对SW480和HCT116细胞的细胞毒性作用。基于线粒体膜电位的降低，Bax的上调，Bcl-2的下调以及caspase-3和9的裂解，Helveticoside通过线粒体介导的内在凋亡信号通路诱导了大肠癌细胞的凋亡。此外，使用p53敲除SW480细胞，发现Helveticoside的细胞毒性作用是p53依赖性的。更重要的是，施用Helveticoside可通过激活细胞凋亡来抑制小鼠HCT116细胞源性结直肠癌异种移植的生长。

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Helveticoside Exhibited p53-dependent Anticancer Activity Against Colorectal Cancer.

BACKGROUND Investigation into the anti-cancer activities of natural products and their derivatives represents an efficient approach to develop safe and effective chemotherapeutic agents for the treatment of colorectal cancer. Helveticoside is a biologically active component of the seed extract of Descurainia sophia. This compound has been reported to regulate the genes related to cell proliferation and apoptosis in lung cancer cells, however its anticancer activity has not been fully explored yet. METHODS Cell viability was evaluated by MTT and Trypan blue exclusion assay; cell apoptosis was measured by flow cytometry; mitochondrial membrane potential was determined by using JC1-mitochondrial membrane potential assay kit; protein levels were determined by western blot assay; in vivo tumor growth was assessed in a xenograft nude mice model. RESULTS The current study demonstrated the in vitro anti-cancer activity of helveticoside against colorectal cancer using colorectal cancer cells SW480 and HCT116. Moreover, induction of apoptosis was found to mediate the cytotoxic action of helveticoside on SW480 and HCT116 cells. Based on the decrease in the mitochondrial membrane potential, upregulation of Bax, downregulation of Bcl-2 and cleavage of caspase-3 and 9, apoptosis was induced by helveticoside via mitochondria-mediated intrinsic apoptotic signaling pathways in colorectal cancer cells. Besides, using p53-knockout SW480 cells, the cytotoxic action of helveticoside was found to be p53-dependent. More importantly, administration of helveticoside inhibited the growth of HCT116 cells derived-colorectal cancer xenograft in mice via activation of apoptosis. CONCLUSIONS Helveticoside might be a potential candidate for the development of novel chemotherapeutic agents for the treatment of colorectal cancer, while the potential toxic effects of helveticoside may be worthy of further investigations.

更新日期：2020-03-06

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