Department of Haematology, University Hospital, Uppsala University, Uppsala, Sweden.
PLoS One. 2011 Jan 5;6(1):e15718. doi: 10.1371/journal.pone.0015718.
Despite years of interest in the anti-cancerous effects of cardiac glycosides (CGs), and numerous studies in vitro and in animals, it has not yet been possible to utilize this potential clinically. Reports have demonstrated promising in vitro effects on different targets as well as a possible therapeutic index/selectivity in vitro and in experimental animals. Recently, however, general inhibition of protein synthesis was suggested as the main mechanism of the anti-cancerous effects of CGs. In addition, evidence of species differences of a magnitude sufficient to explain the results of many studies called for reconsideration of earlier results.
In this report we identified primary B-precursor and T-ALL cells as being particularly susceptible to the cytotoxic effects of CGs. Digitoxin appeared most potent and IC(50) values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC(50) was demonstrated in colorectal tumour cell lines moderately resistant to the cytotoxic effects of digoxin and digitoxin, but not in highly sensitive leukaemia cell lines.
It is suggested that further investigation regarding CGs may be focused on diagnoses like T- and B-precursor ALL.
尽管人们对强心苷（CGs）的抗癌作用产生了多年的兴趣，并在体外和动物身上进行了大量研究，但迄今为止，还无法在临床上利用这一潜力。报告表明，强心苷在不同靶点上具有有希望的体外作用，并且在体外和实验动物中具有可能的治疗指数/选择性。然而，最近有人提出，CGs 的抗癌作用的主要机制是普遍抑制蛋白质合成。此外，有证据表明，种属差异的程度足以解释许多研究的结果，这需要重新考虑早期的结果。
在本报告中，我们发现原发性 B 前体细胞和 T-ALL 细胞特别容易受到 CGs 的细胞毒性作用的影响。地高辛似乎最有效，几个患者样本的 IC（50）值处于可能在临床上达到的浓度范围内。在与地高辛和地高辛的细胞毒性作用的 IC（50）相对应的浓度下，显示出明显的蛋白质合成抑制，而在对地高辛和地高辛高度敏感的白血病细胞系中则没有。
建议进一步研究 CGs 可能集中在 T-和 B-前体细胞 ALL 等诊断上。
