Targeting
cancer cell metabolism is a promising strategy against
cancer. Here, we confirmed that the anti-
cancer drug carboxyamidotriazole (CAI) inhibited mitochondrial respiration in
cancer cells for the first time and found a way to enhance its anti-
cancer activity by further disturbing the energy metabolism. CAI promoted
glucose uptake and
lactate production when incubated with
cancer cells. The oxidative phosphorylation (OXPHOS) in
cancer cells was inhibited by CAI, and the decrease in the activity of the respiratory chain complex I could be one explanation. The anti-
cancer effect of CAI was greatly potentiated when being combined with
2-deoxyglucose (2-DG). The
cancer cells treated with the combination of CAI and 2-DG were arrested in G2/M phase. The apoptosis and
necrosis rates were also increased. In a mouse xenograft model, this combination was well tolerated and retarded the
tumor growth. The impairment of
cancer cell survival was associated with significant cellular
ATP decrease, suggesting that the combination of CAI and 2-DG could be one of the strategies to cause dual inhibition of energy pathways, which might be an effective therapeutic approach for a broad spectrum of
tumors.