Exploring the Anti-Cancer mechanism of Cardiac Glycosides using proteome integral solubility alteration approach

Cancer remains a significant global health challenge, necessitating the development of innovative and cost-effective treatments. Drug repurposing, particularly of cardiac glycosides (CGs), offers a promising strategy to expedite the discovery of anti-tumor drugs. This study employs proteome integral solubility alteration (PISA) to investigate the multifaceted mechanisms of action of CGs, including digoxin, digitoxin, and ouabain. Our study revealed that CGs may interact with a spectrum of proteins associated with cellular metabolism, ribosomal function, and apoptosis, suggesting a complex interplay between these pathways in cancer cells. Besides, it suggests that CGs could be repurposed to target cancer through a multifaceted approach that disrupts cellular metabolism, protein synthesis, and mitochondrial function. Further studies are warranted to confirm the functional implications of these interactions and to explore the therapeutic potential of CGs in cancer treatment.

癌症仍是重大的全球健康挑战，亟需开发创新且经济高效的治疗方案。药物重定位，尤其是强心苷（CGs）的重定位，为加速抗肿瘤药物的发现提供了一种极具前景的策略。本研究采用蛋白质组整体溶解度改变（PISA）技术，探究CGs的多方面作用机制，涉及药物包括地高辛、洋地黄毒苷和哇巴因。研究结果表明，CGs可能与一系列涉及细胞代谢、核糖体功能及凋亡的蛋白质发生相互作用，提示癌细胞中这些通路之间存在复杂的相互调控。此外，研究还提示CGs可通过多维度策略重定位用于癌症治疗，该策略可干扰细胞代谢、蛋白质合成及线粒体功能。需开展进一步研究以明确这些相互作用的功能意义，并探索CGs在癌症治疗中的应用潜力。