Novel strategies of glutathione depletion in photodynamic and chemodynamic therapy: A review

Cancer remains a health problem worldwide; therefore, developing new therapies to increase the effectiveness of anticancer treatments is necessary. Two such methods are photodynamic therapy (PDT) and chemodynamic therapy (CDT). The intensive growth and increased metabolism of tumors lead to elevated levels of reactive oxygen species (ROS) within cancer cells. These cells develop several antioxidant mechanisms to protect them from this oxidative stress. Antioxidants also make tumors more resistant to chemotherapy and radiation. Glutathione (GSH) is an important and the most abundant endogenous cellular antioxidant. Photodynamic therapy and CDT are new methods that are based on the production of ROS,‑ therefore increasing oxidative stress in cancer cells. A significant problem with these therapies is the increased GSH levels, which is an adaptation of cancer cells to augmented metabolic processes. This paper presents various GSH depletion strategies that are used to improve PDT and CDT. While the main goal of GSH depletion in both PDT and CDT is to prevent its interaction with the ROS generated by these therapies, it should be remembered that the reduction of its level itself may initiate pathways leading to cancer cell death.