Abstract
Renal cell carcinomas (RCC) have two types of cells for carbon metabolism and for cell signaling under nutrient-deprivation conditions, namely starvation-resistant and starvation-sensitive cells. Here, we evaluated the mitochondrial characteristics of these cell types and found that the resistant type possessed higher activities for both mitochondrial oxidative phosphorylation and glycolysis than the sensitive types. These higher activities were supported by the stored carbon, lipid and carbohydrate sources, and by a low level of mitochondrial reactive oxygen species (ROS) due to sustained SOD2 expression in the resistant RCC cells. In metastatic RCC cases, higher SOD2 expression was associated with a significantly shorter survival period. We found that treatment with the drugs etomoxir and buformin significantly reduced mitochondrial oxidative phosphorylation and induced cell death under glucose-deprivation conditions in starvation-resistant RCC cells. Our data suggest that inhibitory targeting of mitochondria might offer an effective therapeutic option for metastatic RCC that is resistant to current treatments.
Highlights
Of respiration in starvation-resistant cells compared to sensitive cells that associated with a poorer prognosis
We investigated mitochondrial oxidative phosphorylation in Renal cell carcinoma (RCC) cell lines using XF Cell Mito Stress Test Kit and found that starvation-resistant cells possessed significantly higher spare respiratory capacities than the sensitive cells under glucose-deprivation condition (Fig. 1 and Supplementary Table S1)
These results suggested that starvation-resistant cells possessed higher mitochondrial oxidative phosphorylation activities than sensitive cells
Summary
Of respiration in starvation-resistant cells compared to sensitive cells that associated with a poorer prognosis. Results Starvation-resistant RCC cell lines possess high mitochondrial oxidative phosphorylation activity and abundant glycolytic reserves. We investigated mitochondrial oxidative phosphorylation in RCC cell lines using XF Cell Mito Stress Test Kit and found that starvation-resistant cells possessed significantly higher spare respiratory capacities than the sensitive cells under glucose-deprivation condition (Fig. 1 and Supplementary Table S1).
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