Lowe Lorraine C, Senaratne Siddhika G, Colston Kay W
Department of Cellular and Molecular Medicine, St. George's Hospital Medical School, London, UK.
Biochem Biophys Res Commun. 2005 Apr 8;329(2):772-9. doi: 10.1016/j.bbrc.2005.02.032.
The 1,1-bisphosphonate ester family member apomine (SR-45023A) is known to have anti-tumour activity in various cancer cell types. The aims of this study were to determine the effect of apomine on the growth of two breast cancer cell lines, MCF-7 and MDA-MB-231, to ascertain whether any growth inhibitory effects found were due to induction of apoptosis, and to investigate the mechanism of action of apomine. Apomine caused significant growth inhibition of both cell lines after 72h of treatment. Apomine-induced growth inhibition was associated with caspase and p38 MAPK activation and DNA fragmentation. Apomine had no effect on Ras localisation, nor did addition of mevalonate to treatment media prevent apomine-induced apoptosis. We conclude that apomine induces apoptosis in breast cancer cells, an effect that is independent of oestrogen receptor status and is not via inhibition of the mevalonate pathway. Our study suggests apomine is a potential anti-neoplastic drug in breast cancer treatment.
1,1-二磷酸酯家族成员阿波明（SR-45023A）已知在多种癌细胞类型中具有抗肿瘤活性。本研究的目的是确定阿波明对两种乳腺癌细胞系MCF-7和MDA-MB-231生长的影响，确定所发现的任何生长抑制作用是否归因于凋亡诱导，并研究阿波明的作用机制。处理72小时后，阿波明对两种细胞系均产生显著的生长抑制作用。阿波明诱导的生长抑制与半胱天冬酶和p38丝裂原活化蛋白激酶激活以及DNA片段化有关。阿波明对Ras定位没有影响，在处理培养基中添加甲羟戊酸也不能阻止阿波明诱导的凋亡。我们得出结论，阿波明诱导乳腺癌细胞凋亡，这种作用独立于雌激素受体状态，且不是通过抑制甲羟戊酸途径。我们的研究表明阿波明是乳腺癌治疗中一种潜在的抗肿瘤药物。
