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倍半萜化合物对人类细胞新出现的抗有丝分裂活性及其他生物活性

Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells.

作者信息

Bosco Alessandra, Golsteyn Roy M

机构信息

Natural Product and Cancer Cell Laboratories, Department of Biological Sciences, 4401 University Dr, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.

出版信息

Molecules. 2017 Mar 13;22(3):459. doi: 10.3390/molecules22030459.

Abstract

We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain types of sesquiterpenes can arrest cells in mitosis as measured by cell biology, biochemical and imaging techniques. We have listed the sesquiterpenes that arrest cells in mitosis and analyzed the biological data that support those observations. In view of the biochemical complexity of mitosis, we propose that a subset of sesquiterpenes have a unique chemical structure that can target a precise protein(s) required for mitosis. Since the process of mitotic arrest precedes that of cell death, it is possible that some sesquiterpenes that are currently classified as cytotoxic might also induce a mitotic arrest. Our analysis provides a new perspective of sesquiterpene chemical biology.

摘要

我们综述了天然产物倍半萜的生物活性,并首次描述了它们对有丝分裂的影响。这种对细胞的生物学效应出乎意料,因为倍半萜被认为是通过迈克尔型加成使蛋白质失活,从而导致非特异性细胞毒性。然而,通过细胞生物学、生物化学和成像技术测量发现,某些类型的倍半萜可使细胞停滞于有丝分裂期。我们列出了能使细胞停滞于有丝分裂期的倍半萜,并分析了支持这些观察结果的生物学数据。鉴于有丝分裂的生化复杂性,我们提出一部分倍半萜具有独特的化学结构,能够靶向有丝分裂所需的特定蛋白质。由于有丝分裂停滞过程先于细胞死亡过程,目前被归类为细胞毒性的一些倍半萜也可能诱导有丝分裂停滞。我们的分析为倍半萜化学生物学提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b65a/6155193/ceff4107c49b/molecules-22-00459-g001.jpg

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