Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells
Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells
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DOI：
10.1379/csc-148r.1
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发表时间：
2006-06-01
影响因子：
3.8
通讯作者：
Hatayama, Takumi
中科院分区：
文献类型：
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作者：
Ishihara, Keiichi;Yamagishi, Nobuyuki;Hatayama, Takumi
由于热休克蛋白（Hsps）参与保护细胞以及炎症、癌症和神经退行性疾病等疾病的病理生理学，因此在哺乳动物细胞中使用热休克蛋白表达的调节因子似乎是一种有用的潜在治疗方式。为了确定调节热休克反应的化合物，我们使用含有热休克启动子调节报告基因的哺乳动物细胞系分析了几种天然产物。在本研究中，我们发现牛蒡子提取物明显抑制热休克诱导的热休克蛋白的表达。在热休克转录因子的激活、mRNA的诱导和热休克蛋白的合成和积累水平上，提取物的成分牛蒡子苷（artigenin）而非成分牛蒡子苷（artitin）抑制了热休克反应。此外，牛蒡子素还能抑制哺乳动物细胞（包括癌细胞）的耐热性。因此，自激肽似乎是一种新的抑制哺乳动物细胞热休克反应的调节剂，可能对热疗癌症治疗有用。
Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoter-regulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy.