柠檬酸盐通过促进细胞凋亡增强表观遗传学治疗的潜力。
The potential for citrate to reinforce epigenetic therapy by promoting apoptosis.
机构信息
Normandie University, UNICAEN, INSERM U1086 Interdisciplinary Research Unit for Cancer Prevention and Treatment, Caen, France; Service de Chirurgie Thoracique, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Université Paris-Descartes, Paris, France.
Service de Chirurgie Thoracique, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Université Paris-Descartes, Paris, France; INSERM U1138, Integrative Cancer Immunology, University of Paris, 75006 Paris, France.
出版信息
Trends Endocrinol Metab. 2023 Oct;34(10):586-589. doi: 10.1016/j.tem.2023.07.002. Epub 2023 Aug 5.
Epigenetic drugs induce ATP depletion, promoting a glycolysis-to-oxidative phosphorylation (OXPHOS) shift which sometimes favors tumor growth by promoting necroptosis over apoptosis. To restore effective apoptosis in tumors, we propose that the administration of citrate could inhibit ATP production, activate caspase-8 (a key necroptosis inhibitor), and downregulate key anti-apoptotic proteins (Bcl-xL and MCL1).
表观遗传药物诱导 ATP 耗竭，促进糖酵解向氧化磷酸化（OXPHOS）转变，有时通过促进坏死性凋亡而不是细胞凋亡来促进肿瘤生长。为了恢复肿瘤中有效的细胞凋亡，我们提出可以通过给予柠檬酸盐来抑制 ATP 的产生，激活半胱天冬酶-8（一种关键的坏死性凋亡抑制剂），并下调关键的抗凋亡蛋白（Bcl-xL 和 MCL1）。
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