Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway
Cytotoxic mechanism of novel compound jiangxienone from Cordyceps jiangxiensis against cancer cells involving DNA damage response pathway
复制标题
江西冬虫夏草新型化合物江西烯酮对癌细胞的细胞毒作用机制涉及DNA损伤反应途径
DOI：
10.1016/j.procbio.2014.01.027
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Zhong, Jian-Jiang
中科院分区：
文献类型：
--
作者：
Lu, Yu-Hong;Pan, Wei-Dong;Zhong, Jian-Jiang
江西烯酮是最近从传统中药用蘑菇江西冬虫夏草中纯化出来的一种新型化合物，据报道对癌细胞表现出强大的细胞毒性。然而，其作用机制仍不清楚。在这项工作中，利用全基因组微阵列研究了江西烯酮对抗人胃癌细胞HGC-27的潜在机制。结果表明，江西烯酮能显着减少多种人类癌细胞系的细胞数量，同时即使在高浓度下也能轻微抑制小鼠骨髓基质细胞的集落形成。差异基因表达谱表明，江西烯酮对 HGC-27 的细胞毒作用与 DNA 损伤反应途径密切相关，通过鉴定 XRCC4/5/6、NBS1、RAD51 和 BRAI/2 等 23 个 DNA 损伤反应相关基因证明了这一点。通过凝胶延迟测定、紫外吸收光谱和单细胞凝胶电泳，发现江西烯酮可以与DNA结合并抑制癌细胞生长。上述结果表明，姜西烯酮对癌细胞的细胞毒作用机制涉及DNA损伤反应途径。这些发现将有助于从江西 C. Jiangxiensis 中开发有用的癌症化学预防化合物。 (C) 2014 Elsevier Ltd. 保留所有权利。
Jiangxienone is a novel compound recently purified from the traditional Chinese medicinal mushroom Cordyceps jiangxiensis and was reported to show potent cytotoxicity against cancer cells. However, its mechanism of action remains unclear. In this work, the underlying mechanism of jiangxienone against human gastric cancer cells HGC-27 was investigated using whole-genome microarray. The results demonstrated that jiangxienone significantly decreased cell population of various human cancer cell lines, while slightly inhibited the colony formation of stromal cells from murine marrow even at a high concentration. Differential gene expression profiling indicated that the cytotoxic action of jiangxienone against HGC-27 is closely related to the DNA damage response pathway, which was evident by the identification of 23 DNA damage response-associated genes, such as XRCC4/5/6, NBS1, RAD51, and BRCAI/2. By using gel retardation assays, UV absorption spectrometry and single-cell gel electrophoresis, it was found that jiangxienone could bind to DNA and inhibit cancer cell growth. The above results indicated that the cytotoxic mechanism of jiangxienone against cancer cells was involved in the DNA damage response pathway. The findings will be helpful to the development of useful cancer chemopreventive compounds from C. jiangxiensis. (C) 2014 Elsevier Ltd. All rights reserved.