皮肤 T 细胞淋巴瘤 (CTC) 是一组异质性皮肤 T 细胞淋巴增殖性恶性肿瘤，治疗选择有限，但抵抗力和缓解率增加。代谢重编程对于协调癌细胞不受控制的生长和增殖至关重要。重要的是，失调的信号传导在代谢重编程中发挥着重要作用。考虑到代谢重编程在癌细胞生长和增殖中的关键作用，靶点识别和新型多靶点药物的开发势在必行。本研究探讨了光甘草定介导的 CTCL 抗癌作用的潜在机制和代谢信号通路。我们的结果表明，光甘草定通过诱导细胞程序性死亡（PCD），如细胞凋亡、自噬和坏死，显着抑制 CTCL 细胞的生长。有趣的是，结果进一步表明光甘草定通过靶向 MAPK 信号通路，特别是 ERK 的激活，诱导 CTCL 细胞中的 PCD。此外，光甘草定还使 CTCL 细胞对抗癌药物硼替佐米敏感。重要的是，基于 LC-MS 的代谢组学分析进一步表明，光甘草定以 ERK 依赖性方式靶向与癌细胞生长和增殖错综复杂的多种代谢物和代谢途径。总体而言，我们的研究结果表明，光甘草定可诱导 PCD 并减弱调节蛋白和代谢物的表达，这些调节蛋白和代谢物参与通过 ERK 激活来协调 CTCL 细胞不受控制的增殖。因此，光甘草定具有理想抗癌剂的重要特征。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Cutaneous T-cell lymphomas (CTC) are a heterogeneous group of T-cell lymphoproliferative malignancies of the skin with limited treatment options, increased resistance and remission. Metabolic reprogramming is vital in orchestrating the uncontrolled growth and proliferation of cancer cells. Importantly, deregulated signalling plays a significant role in metabolic reprogramming. Considering the crucial role of metabolic reprogramming in cancer-cell growth and proliferation, target identification and the development of novel and multi-targeting agents are imperative. The present study explores the underlying mechanisms and metabolic signalling pathways associated with Glabridin mediated anti-cancer actions in CTCL. Our results show that Glabridin significantly inhibits the growth of CTCL cells through induction of programmed cell death (PCD) such as apoptosis, autophagy and necrosis. Interestingly, results further show that Glabridin induces PCD in CTCL cells by targeting MAPK signalling pathways, particularly the activation of ERK. Further, Glabridin also sensitized CTCL cells to the anti-cancer drug, bortezomib. Importantly, LC-MS-based metabolomics analyses further showed that Glabridin targeted multiple metabolites and metabolic pathways intricately involved in cancer cell growth and proliferation in an ERK-dependent fashion. Overall, our findings revealed that Glabridin induces PCD and attenuates the expression of regulatory proteins and metabolites involved in orchestrating the uncontrolled proliferation of CTCL cells through ERK activation. Therefore, Glabridin possesses important features of an ideal anti-cancer agent.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.