Jaiswal Apurva, Kaushik Neha, Patel Paritosh, Acharya Tirtha Raj, Mukherjee Subhadip, Choi Eun Ha, Kaushik Nagendra Kumar
Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, South Korea.
Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong, 18323, South Korea.
Free Radic Biol Med. 2025 Mar 1;229:264-275. doi: 10.1016/j.freeradbiomed.2024.12.045. Epub 2024 Dec 24.
Glioblastoma (GBM) remains a formidable clinical challenge, with cancer stem cells (CSCs) contributing to treatment resistance and tumor recurrence. Conventional treatments often fail to eradicate these CSCs characterized by enhanced resistance to standard therapies through metabolic plasticity making them key targets for novel treatment approaches. Addressing this challenge, this study introduces a novel combination therapy of dichloroacetate (DCA), a metabolic modulator and nonthermal plasma to induce oxidative stress in glioblastomas. Our results demonstrate that DCA and nonthermal plasma (NTP) synergistically increase ROS production, resulting in endoplasmic reticulum (ER) stress and mitochondrial reprogramming, key factors in the initiation of programmed cell death. Furthermore, the combination downregulated key stemness markers indicating effective CSCs suppression. Upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic factors highlight the induction of apoptosis in glioma stem cells. This study provides compelling evidence that the combination of DCA and NTP offers a novel and effective strategy for targeting glioma CSCs by inducing oxidative and metabolic stress, underscoring potential therapeutic advancements in glioblastoma treatment.
胶质母细胞瘤（GBM）仍然是一项严峻的临床挑战，癌症干细胞（CSCs）导致治疗耐药性和肿瘤复发。传统治疗往往无法根除这些癌症干细胞，它们通过代谢可塑性对标准疗法具有更强的耐药性，这使得它们成为新型治疗方法的关键靶点。为应对这一挑战，本研究引入了一种新型联合疗法，即使用代谢调节剂二氯乙酸（DCA）和非热等离子体来诱导胶质母细胞瘤中的氧化应激。我们的结果表明，DCA和非热等离子体（NTP）协同增加活性氧（ROS）的产生，导致内质网（ER）应激和线粒体重编程，这是程序性细胞死亡启动的关键因素。此外，联合疗法下调了关键的干性标志物，表明对癌症干细胞有有效的抑制作用。促凋亡蛋白的上调和抗凋亡因子的下调突出了胶质瘤干细胞中凋亡的诱导。本研究提供了令人信服的证据，表明DCA和NTP的联合通过诱导氧化和代谢应激为靶向胶质瘤癌症干细胞提供了一种新颖且有效的策略，强调了胶质母细胞瘤治疗中潜在的治疗进展。
