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首页> 外文期刊>The Journal of Antibiotics: An International Journal >GEX1 Compounds, Novel Antitumor Antibiotics Related to Herboxidiene, Produced by Streptomyces sp. II. The Effects on Cell Cycle Progresion and Gene Expression
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GEX1 Compounds, Novel Antitumor Antibiotics Related to Herboxidiene, Produced by Streptomyces sp. II. The Effects on Cell Cycle Progresion and Gene Expression

机译：GEX1化合物，与草氧化烯有关的新型抗肿瘤抗生素，由链霉菌属产生。二。对细胞周期进展和基因表达的影响

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摘要

Six GEX1 compounds, GEX1A/herboxidiene and its related 5 novel compounds, were isolaetd from a culture broth of Streptomyces sp. GEX1 compounds induced both G1 and G2/M arrest in a human normal fibroblast cell line, WI-38.All six compounds up-regulated luciferase reporter gene expression directed by enhancer/promoter of various genes, such as cdc2, IL-2 and SV40 early genes. All GEX1 compounds showed cytotoxic activities in the same order of the up-regulating activitieson gene expression, suggesting that these two activities are related. Despite the up-regulating activities on the reporter gene expression, GEX1A/herboxidine did not enhance the expression of any endogenous genes involved in the cell cycle, proliferation and apoptosis. Although the unique effects of GEX1 compounds on cell cycle and the reporter gene expression were similar to those of trichostain A (TSA), an inhibitor of histone decetylase (HDAC), GEX1A/herboxidene did not affect histone acetylation in cells. In addition, GEX1A/herboxidiene treatment gave rise to the shorter sized transcripts of the cdc25A and cdc2 genes as well as the normal sized ones. These results suggest that GEX1 compounds modulate gene expressioin by an unknown mechanism.
机译：从Streptomyces sp。的培养液中分离了6种GEX1化合物GEX1A / herboxidiene及其相关的5种新化合物。 GEX1化合物可诱导人正常成纤维细胞WI-38中的G1和G2 / M阻滞。所有六种化合物均上调萤光素酶报告基因的表达，这些基因由各种基因（例如cdc2，IL-2和SV40的增强子/启动子）指导。早期基因。所有GEX1化合物均以与基因表达上调活性相同的顺序显示细胞毒性活性，表明这两种活性是相关的。尽管对报告基因的表达有上调活性，但GEX1A / herboxidine并未增强任何参与细胞周期，增殖和凋亡的内源基因的表达。尽管GEX1化合物对细胞周期和报告基因表达的独特作用类似于三糖化蛋白A（TSA），即组蛋白去甲酰化酶（HDAC）的抑制剂，但GEX1A /草丹烯不影响细胞中的组蛋白乙酰化。此外，GEX1A / herboxidiene处理产生了cdc25A和cdc2基因以及正常大小的转录本较短的转录本。这些结果表明，GEX1化合物通过未知机制调节基因表达。

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