Glutathione and Cancer

 

At present, the effective treatment of cancer still faces great challenges. In order to resist oxidative stress damage caused by a large amount of reactive oxygen species (ROS) produced during cancer development, cancer cells usually have higher levels of antioxidant systems.

Glutathione (GSH) is one of the most important antioxidants in the cellular antioxidant system. Studies have shown that the absence of GSH disrupts the redox homeostasis of cells, leads to the accumulation of ROS, and eventually triggers cell damage and even death.

For cancer cells, high levels of oxidative stress make them more sensitive to GSH loss, a vulnerability that could be exploited for cancer therapy.

Currently, research on GSH depletion strategies for cancer therapy mainly includes three aspects:

1) Enhance the efficacy of ROS therapy by reducing the clearance of ROS by GSH. The therapies involved mainly include photodynamic therapy (PDT), sonodynamic therapy (SDT) and chemodynamic therapy (CDT). ROS therapy targets the delivery of specific active substances to cancer tissues, and generates a large amount of ROS under the activation of light, ultrasound or chemical reactions, thereby triggering cell death. However, the scavenging effect of ROS by high levels of GSH in cancer cells reduces its expected efficacy, so many studies have combined ROS therapy with GSH depletion strategies to improve the efficacy of the original therapy;

2) Improve the efficacy of chemotherapy drugs by reducing the detoxification effect of GSH. Commonly used chemotherapeutic drugs such as cisplatin, doxorubicin, chlorambucil, etc. are the targets of GSH detoxification. cell efflux. This detoxification process will significantly weaken the efficacy of chemotherapy drugs, and even lead to the occurrence of drug resistance. A large number of studies have proved that reducing the level of GSH in cancer cells can successfully improve the efficacy of chemotherapy drugs against multiple drug-resistant tumors;

3) Induce cancer cell death by means of ferroptosis. Ferroptosis is an iron ion-dependent cell death mode discovered in recent years. Its main feature is the accumulation of lipid peroxides caused by the imbalance between the generation and degradation of lipid peroxides in cells. Glutathione peroxidase 4 (GPX4) is a key enzyme in the degradation process of lipid peroxides. Since GSH is a reducing co-substrate of GPX4, depletion of GSH can inactivate GPX4 and induce lipid peroxidation, thereby inducing ferroptosis in cells.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.