Menger Laurie, Vacchelli Erika, Kepp Oliver, Eggermont Alexander, Tartour Eric, Zitvogel Laurence, Kroemer Guido, Galluzzi Lorenzo
Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre, France ; INSERM; U848; Villejuif, France.
Oncoimmunology. 2013 Feb 1;2(2):e23082. doi: 10.4161/onci.23082.
Cardiac glycosides (CGs) are natural compounds sharing the ability to operate as potent inhibitors of the plasma membrane Na/K-ATPase, hence promoting-via an indirect mechanism-the intracellular accumulation of Ca ions. In cardiomyocytes, increased intracellular Ca concentrations exert prominent positive inotropic effects, that is, they increase myocardial contractility. Owing to this feature, two CGs, namely digoxin and digitoxin, have extensively been used in the past for the treatment of several cardiac conditions, including distinct types of arrhythmia as well as contractility disorders. Nowadays, digoxin is approved by the FDA and indicated for the treatment of congestive heart failure, atrial fibrillation and atrial flutter with rapid ventricular response, whereas the use of digitoxin has been discontinued in several Western countries. Recently, CGs have been suggested to exert potent antineoplastic effects, notably as they appear to increase the immunogenicity of dying cancer cells. In this Trial Watch, we summarize the mechanisms that underpin the unsuspected anticancer potential of CGs and discuss the progress of clinical studies that have evaluated/are evaluating the safety and efficacy of CGs for oncological indications.
强心苷（CGs）是一类天然化合物，具有作为质膜钠/钾-ATP酶强效抑制剂的作用，因此通过间接机制促进钙离子在细胞内的积累。在心肌细胞中，细胞内钙离子浓度升高会产生显著的正性肌力作用，即增强心肌收缩力。由于这一特性，过去两种强心苷，即地高辛和洋地黄毒苷，被广泛用于治疗多种心脏疾病，包括不同类型的心律失常以及收缩功能障碍。如今，地高辛已获美国食品药品监督管理局（FDA）批准，用于治疗充血性心力衰竭、伴有快速心室反应的心房颤动和心房扑动，而在一些西方国家，洋地黄毒苷的使用已被停止。最近，有人提出强心苷具有强大的抗肿瘤作用，特别是因为它们似乎能增加垂死癌细胞的免疫原性。在本试验观察中，我们总结了支撑强心苷未被怀疑的抗癌潜力的机制，并讨论了评估/正在评估强心苷用于肿瘤适应症的安全性和有效性的临床研究进展。
