Table 1.
EA cytotoxicity correlates with glucose sensitivity in a panel of cell lines.
| Cell line | Origin of the Tissue | EA (IC50) | 2-DG (IC50) |
|---|---|---|---|
| 786-0 | Kidney cancer (VHL−/−) (Williams et al., 1978) | 50 nM | 60 μM |
| 786-0/VHL | VHL-restored cell line (Tong et al., 2011) | >10 μM | >1 mM |
| UOK257 | Kidney cancer (FLCN−/−) (Yang et al., 2008) | 65 nM | 285 μM |
| UOK257WT | FLCN-restored cell line (Hong et al., 2010) | >10 μM | 721 μM |
| UOK262 | Kidney cancer metastasis(FH−/−) (Yang et al., 2010) | 35 nM | 222 μM# |
| UOK262WT | FH-restored cell line (Tong et al., 2011) | >10 μM | >1 mM# |
| HK2 | Normal Kidney (proximal tubule) (Ryan et al., 1994) | >10 μM | >1 mM |
| HEK293 | Embryonic epithelial Kidney cell (Pear et al., 1993) | >10 μM | >1 mM |
| PC3 | Prostate cancer (Kaighn et al., 1979) | 5 μM | 300 μM |
| SKBr3 | Breast cancer (J. Fogh and G. Trempe, 1975) | 3 μM | n/a |
Cells (70% confluence) were treated with a range of EA concentrations (1 nM – 10 μM) in serum-free media. After 48 h, viability was measured by MTT or manual cell counting. For UOK262 and UOK262WT, viability was only assessed by manual cell counting. Molecularly restored kidney cancer cell lines and normal kidney cell lines did not show significant sensitivity towards EA. Glucose dependence of the cells was similarly assessed by determining sensitivity to 2-deoxyglucose (2-DG, 10 nM –100 μM). Cells were cultured in DMEM containing 1g/L glucose and were treated with 2-DG for 72 h (786-0, 786-0/VHL, UOK257, UOK257WT, HK2, HEK293, PC3, and SKBr3),
except for UOK262 and UOK262WT which were treated for 24 h. Viability was assessed by MTT and/or manual cell counting as above. EA sensitivity displays a highly significant positive correlation with glucose dependence, as assessed by determining R2 and the Pearson Correlation Coefficient (R2 = 0.9126; Pearson Correlation Coefficient = 0.962; p = 0.000003). UOK262 data were not included when determining R2 and the Pearson Correlation Coefficient because they were exposed to 2-DG for 24 h and not 72 h like the other cell lines.