Nonthermal Plasma Boosted Dichloroacetate Induces Metabolic Shifts to Combat Glioblastoma CSCs via Oxidative Stress.

in Free radical biology & medicine by Apurva Jaiswal, Neha Kaushik, Paritosh Patel, Tirtha Raj Acharya, Subhadip Mukherjee, Eun Ha Choi, Nagendra Kumar Kaushik

TLDR

  • The study demonstrates a novel combination therapy of DCA and NTP that synergistically targets glioma CSCs by inducing oxidative stress, ER stress, and mitochondrial reprogramming.
  • The combination therapy shows promising results in suppressing CSCs and inducing apoptosis in glioma cells.
  • The study highlights the potential therapeutic applications of the combination therapy for improving treatment outcomes in patients with glioblastoma.

Abstract

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 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.

Overview

  • The study focuses on the treatment of glioblastoma (GBM) by targeting cancer stem cells (CSCs) with a novel combination therapy of dichloroacetate (DCA) and nonthermal plasma (NTP).
  • The study aims to investigate the synergistic effects of DCA and NTP in inducing oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial reprogramming in glioma cells, leading to the suppression of CSCs.
  • The primary objective is to develop a novel treatment strategy for glioblastoma by inducing apoptosis and oxidative stress in glioma cells, thereby targeting CSCs and improving treatment outcomes.

Comparative Analysis & Findings

  • The study demonstrated that the combination of DCA and NTP synergistically increases reactive oxygen species (ROS) production, leading to ER stress and mitochondrial reprogramming.
  • The combination therapy showed effective suppression of CSCs by downregulating key stemness markers, upregulating pro-apoptotic proteins, and downregulating anti-apoptotic factors.
  • The results highlight the potential therapeutic applications of the combination therapy for targeting glioma CSCs and improving treatment outcomes in patients with glioblastoma.

Implications and Future Directions

  • The study suggests that the combination of DCA and NTP may offer a novel and effective strategy for targeting glioma CSCs, which is a critical step towards improving treatment outcomes in patients with glioblastoma.
  • Future studies should investigate the optimal dosing regimens and combination schedules of DCA and NTP to maximize their therapeutic effects in glioblastoma patients.
  • The study underscores the need for further research on the molecular mechanisms underlying the synergistic effects of DCA and NTP, which may lead to the development of new treatment strategies for glioblastoma.
Read Full Article