Bioenergetics of Human Cancer Cells and Normal Cells

Cancer cells are known to have different metabolic properties than normal cells, particularly their tendency to undergo glycolysis even under aerobic favoring conditions. This has created interest in how mitochondrial function in tumor cells may differ from that in normal cells. Using human malignant cells (SW-620, PC-3, HT-1080, SK-MEL, HL-60, K-562 and MOLT-3), human fibroblast (CCL-153) and human T Cells, we investigated three key parameters that have been typically to describe mitochondrial function: cellular ATP production, mitochondrial potential and cellular cardiolipin levels. On average, tumor cancer cells had more ATP production and greater mitochondrial potentials. For example, ATP levels in malignant cells ranged from 20 to 69 μmole/106 cells, with a cancer cell average of 40 ± 18 μmole/106 cells. For normal cells, the ATP level range went from 9 to 24 μmole/106 cells, for an average of 15 ± 11 μmole/106 cells. Mitochondrial potentials tended to be three times higher in cancer cells, perhaps because overall mitochondrial mass (as measured by relative cardiolipin levels) were twice as high in cancer cells. Higher mitochondrial masses are consistent with proliferation. Proliferating cells in general showed higher mitochondrial function compared to quiescent cells (confluent monolayers), and HL-60 cells showed reductions in all three mitochondrial parameters measured here when the cells were exposed to the differentiating agent TPA. The effects of ATP production inhibitors CCCP and oligomycin on mitochondrial function in normal and cancer cells were also compared. In general, in these experiments, cancer cell mitochondrial inhibition with these agents produced a decrease ATP levels by 30-40% while in normal cells ATP production was reduced by 60%. These results provideevidence of a mitochondrial dysfunction in cancer cells. Cancer cells appear to better withstand interference with ATP synthesis in mitochondria since they rely mainly on glycolysis as an energy producing mechanism.