Winnicka Katarzyna, Bielawski Krzysztof, Bielawska Anna
Department of Pharmaceutical Technology, Medical University of Białystok, 1 Kilińskiego Str., 15-089 Białystok, Poland.
Acta Pol Pharm. 2006 Mar-Apr;63(2):109-15.
The well known and accepted mode of action of cardiac glycosides is inhibition of the ubiquitous plasma membrane Na+, K+-ATPase that leads to increased intracellular Ca2+ ion concentrations. Ca2+ ions play pivotal role in many signaling pathways including those regulating apoptosis. It has been suggested that some forms of cardiac glycosides inhibit proliferation and induce apoptosis in prostate cancer cells in clinically relevant concentrations. It was also found out that the degree to which cardiac glycosides inhibited cancer cell growth was correlated to topoisomerase II-inhibiting activity. Digitoxin at concentrations found in cardiac patients induced levels of DNA-topoisomerase II cleavable complexes similar to etoposide, a topoisomerase II poison widely used in cancer chemotherapy. Cardiac glycosides can also regulate one of the most potent angiogenesis promoting substances, fibroblast growth factor-2 (FGF-2), and may inhibit activation of the transcription factor NF-kappaB. FGF-2 and NF-kappaB are relevant targets for anticancer drugs. There is growing interest in evaluating the oleander products and possibly other cardiac glycosides as antineoplastic agents. The first of these therapies to be developed in the United States is a patented, water-soluble oleander extract called Anvirzel.
强心苷广为人知且被认可的作用方式是抑制普遍存在的质膜钠钾ATP酶，这会导致细胞内钙离子浓度升高。钙离子在包括调节细胞凋亡的信号通路在内的许多信号通路中起关键作用。有人提出，某些形式的强心苷在临床相关浓度下可抑制前列腺癌细胞的增殖并诱导其凋亡。还发现强心苷抑制癌细胞生长的程度与拓扑异构酶II抑制活性相关。在心脏病患者体内发现的洋地黄毒苷浓度所诱导的DNA拓扑异构酶II可切割复合物水平与依托泊苷相似，依托泊苷是一种广泛用于癌症化疗的拓扑异构酶II毒药。强心苷还可调节最有效的促血管生成物质之一成纤维细胞生长因子-2（FGF-2），并可能抑制转录因子NF-κB的激活。FGF-2和NF-κB是抗癌药物的相关靶点。人们对评估夹竹桃产品以及可能的其他强心苷作为抗肿瘤药物的兴趣与日俱增。在美国开发的这些疗法中的第一种是一种名为Anvirzel的专利水溶性夹竹桃提取物。
