Description
Gliotoxin was initially produced by the marine fungus Aspergillus and exhibits anticancer, immunosuppressive, and anti-fibrotic activities. In cervical cancer and chondrosarcoma cells, gliotoxin increases activation of caspases 3, 8, and 9, upregulates Bax, and downregulates Bcl-2, resulting in release of cytochrome c and apoptosis. In hepatoma cells, gliotoxin inhibits activation of NF-κB, p38, and Gadd45a, potentiating the effects of radiation and inhibiting cell proliferation. Gliotoxin also suppresses the adaptive immune response, decreasing ROS generation, inhibiting phagocytosis, and inducing apoptosis in leukocytes. Gliotoxin induces a thiol redox-dependent alteration in adenine nucleoside transporter (ANT) mobility and increases activation of caspase 3 and release of cytochrome c, resulting in mitochondria-mediated apoptosis in hepatic stellate cells. This compound also displays anti-parasitic and antimalarial activities against Plasmodium falciparum, inhibiting the proteasome.