Cancer Grows on SOD1
A report in the Proceedings of the National Academy of Sciences shows how superoxide dismutase 1 acts as a master regulatory switch for kinase phosphorylation in angiogenesis and cell proliferation, making it a potential target to treat a variety of cancers.1 Although some mechanistic details remain to be elucidated, superoxide dismutase 1 inhibition could be used in combination with other cancer treatments and might have utility in some degenerative diseases as well.
Superoxide dismutase 1 (SOD1) is one of three SOD enzymes that catalyze the conversion of intracellular superoxide to hydrogen peroxide. Intracellular superoxide is produced when a growth factor binds to its receptor on the cell surface and induces receptor phosphorylation (see Figure 1, "Superoxide dismutase 1 in cancer").
Recently, SOD1 was identified as the target of tetrathiomolybdate (TTM),2 a compound that has antiangiogenic and antitumor activity in mice,3-5but whose mechanism of action remained unclear.
In the PNASpaper, short interfering RNA and ATN-224, a second-generation TTM from Attenuon LLC, were used to study SOD1 inhibition in human umbilical vein endothelial cells (HUVECs) and multiple myeloma (MM) tumor cells.