Fig 1.
Chemical structures of the studied non-nucleoside reverse transcriptase inhibitors.
Fig 2.
Apoptosis and necrosis induction in cancer cells by non-nucleoside reverse transcriptase inhibitors.
The fraction of apoptotic and necrotic cells after treatment with different NNRTIs in different concentrations was measured by Annexin-V-APC/7AAD staining and flow cytometry. An example of the gating in the FACS plots is shown for untreated (a) and with a toxic concentration of EFV treated cells (b). A curve was fitted through the data points of the total fraction of dead cells and the EC50 was calculated for each drug. The pancreatic cancer cell line BxPC-3 was treated for 72h with (c) EFV, (d) NVP, (e) RPV, (f) ETR, (g) LSV and (h) DLV. The pancreatic cancer cell line Panc-1 was treated for 72h with (j) EFV, (k) NVP and (l) RPV.
Fig 3.
Effect of EFV, NVP and RPV on the survival fraction of cancer cells.
Colony formation assays were performed with (a) EFV, (b) NVP and (c) RPV. The pancreatic cancer cell line BxPC-3 was treated for 72h with each of the drugs. The survival fraction (SF) was analyzed and normalized to the control. Graphs were fitted and the EC50 was calculated.
Fig 4.
Comparison of blood levels in patients with in vitro toxic EC50 of EFV, NVP and RPV.
Blood levels of (a) EFV, (b) NVP and (c) RPV determined by HPLC (bars). These in vivo concentrations are compared to the fitted function of the in vitro toxicity against BxPC-3 pancreatic cancer cells in the Annexin-V-APC/AAD staining (solid line).
Table 1.
Blood levels of various NNRTIs.