Gastric cancer is one of the most common human
malignancies, and its prevalence has been shown to be well-correlated with
cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the
cancer has already metastasized. Recent research has emphasized the identification of
cancer biomarkers in the hope of diagnosing
cancer early and designing targeted
therapies to reverse
cancer progression. One member of a family of growth-related
nicotinamide adenine dinucleotide (
NADH or
hydroquinone)
oxidases is
tumor-associated NADH oxidase (tNOX; ENOX2). Unlike its counterpart CNOX (ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by
growth factors and
hormones, tNOX activity purified from rat
hepatoma cells is constitutively active. Its activity is detectable in the sera of
cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, tNOX expression was shown to be present in an array of
cancer cell lines. More importantly, inhibition of tNOX was well correlated with reduced
cancer cell growth and induction of apoptosis. RNA interference targeting tNOX expression in
cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of tNOX in
cancer cells. Here, we review the regulatory role of tNOX in
gastric cancer cell growth.