Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore.
Cancer Lett. 2014 Apr 28;346(1):94-103. doi: 10.1016/j.canlet.2013.12.023. Epub 2013 Dec 24.
In this paper we show that acetyltanshinone IIA (ATA), a novel anti-cancer agent, preferentially inhibits cell growth of oestrogen receptor positive (ER+) breast cancer cells and that it is more potent than the commonly used anti-breast cancer agent, tamoxifen. The metabolic product of ATA, hydroquinone tanshinone IIA (HTA) binds to the ERα and causes its degradation mainly in the nucleus via an ubiquitin-mediated proteasome-dependent pathway. In addition, ATA also reduced the mRNA levels of the ERα encoding gene, ESR1, distinguishing ATA from another anti-breast cancer drug, fulvestrant. Finally, ATA reduced the transcription of an ER-responsive gene, GREB1.
在本文中，我们证明了新型抗癌药物乙酰丹参酮 IIA（ATA）优先抑制雌激素受体阳性（ER+）乳腺癌细胞的生长，其效力强于常用的乳腺癌治疗药物他莫昔芬。ATA 的代谢产物对苯二酚丹参酮 IIA（HTA）与 ERα 结合，并通过泛素介导的蛋白酶体依赖性途径主要在核内导致其降解。此外，ATA 还降低了 ERα 编码基因 ESR1 的 mRNA 水平，这使 ATA 有别于另一种乳腺癌药物氟维司群。最后，ATA 降低了 ER 反应性基因 GREB1 的转录。
