Cytoglobin is a recently identified vertebrate
globin whose functions include scavenging reactive
oxygen and nitrosative species. In
tumor cells, CYGB may function as a tumor suppressor gene. Here we show that knockdown of
cytoglobin expression can sensitize human
glioma cells to oxidative stress induced by chemical inhibitors of the electron transport chain and as well can increase cellular radiosensitivity. When treated with
antimycin A, an inhibitor of the mitochondrial electron transport chain,
cytoglobin-deficient cells showed significantly higher H₂O₂ levels, whereas H₂O₂ levels were significantly reduced in
cytoglobin-overexpressing cells. In addition,
cytoglobin knockdown significantly decreased the doubling time of
glioma cell lines, consistent with a putative
tumor suppressor function. These finding suggest that modulating
cytoglobin levels may be a promising treatment strategy for sensitizing human
glioma cells to oxidative stress that is induced by ionizing radiation, certain
chemotherapies and
ischemia-reperfusion.