GLUTATHIONE: INDUCTION OF APOPTOSIS AND AUTOPHAGY IN CANCER

Glutathione (GSH) is the most abundant non-protein thiol in eukaryotic cells capable of carrying out antioxidant defense mechanisms in the cell for its survivability, mostly against free radicals, i.e., Reactive Oxygen Species (ROS). GSH protects normal cells against carcinogenic transformation, but high GSH levels in cancer cells decrease sensitivity to chemo- and radiotherapy, producing resistant cases of cancer. Hence, GSH depletion could be a potential mechanism by which resistant tumor cells can be sensitized to undergo apoptosis and autophagy. Thiol oxidation leads to the formation of permeability transition pore, promoting the extrusion of death-related molecular signals and activation of the intrinsic apoptotic pathway. Similarly, macroautophagic cell death involves the formation of auto-phagosomes that degrade organelles, including mitochondria, compromising normal cellular function and cellular death occurs by mechanisms such as mTorC1 inhibition. Therefore, the selective depletion of GSH in cancer cells could offer a promising approach in drug and radiation-resistant cases targeting multiple death-related cellular pathways. However, the selective depletion of such ubiquitous antioxidant, GSH in cancer cells yet remains to be a key challenge to the researchers worldwide.