Zhou Lingli, Chan W K, Xu Naihan, Xiao Kang, Luo Houwei, Luo Kathy Qian, Chang Donald C
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Life Sci. 2008 Sep 12;83(11-12):394-403. doi: 10.1016/j.lfs.2008.07.011. Epub 2008 Jul 31.
Tanshinone IIA (Tan IIA) is a compound isolated from Salvia miltiorrhiza Bunge (Danshen). The aim of this study is to investigate the mechanisms of its anti-cancer effect.
To clearly delineate the cell cycle-dependent effects of Tan IIA, we used either synchronized cells or single living cell analysis to conduct our studies. Subcellular fractionation, Western blot analysis, immuno-fluorescence staining and FACS analysis were also employed in our study.
We found that Tan IIA could arrest cancer cells in mitosis by disrupting the mitotic spindle and subsequently triggered cells to enter apoptosis through the mitochondria-dependent apoptotic pathway. Thus, Tan IIA could selectively kill mitotic cells over interphase cells. In comparison with other existing anti-cancer drugs that cause mitotic arrest by interfering with the microtubule structure (such as vincristine or taxol), Tan IIA destroyed only the mitotic spindle during the M phase but not the microtubule structure in interphase cells. Furthermore, Tan IIA could trigger the mitotic arrested cells to enter apoptosis faster than vincristine or taxol.
Since Tan IIA can selectively induce cancer cells to enter apoptosis through mitotic arrest, it has the potential to be developed into an anti-cancer drug.
丹参酮IIA（Tan IIA）是从丹参中分离出的一种化合物。本研究旨在探讨其抗癌作用机制。
为明确Tan IIA对细胞周期的依赖性作用，我们使用同步化细胞或单细胞活体分析进行研究。本研究还采用了亚细胞分级分离、蛋白质免疫印迹分析、免疫荧光染色和流式细胞术分析。
我们发现Tan IIA可通过破坏有丝分裂纺锤体使癌细胞停滞于有丝分裂期，随后通过线粒体依赖性凋亡途径触发细胞凋亡。因此，Tan IIA对处于有丝分裂期的细胞的杀伤作用强于间期细胞。与其他通过干扰微管结构导致有丝分裂停滞的现有抗癌药物（如长春新碱或紫杉醇）相比，Tan IIA仅在M期破坏有丝分裂纺锤体，而不破坏间期细胞的微管结构。此外，Tan IIA比长春新碱或紫杉醇能更快地促使有丝分裂停滞的细胞进入凋亡。
由于Tan IIA可通过有丝分裂停滞选择性诱导癌细胞凋亡，它有潜力被开发成为一种抗癌药物。
