Table 1. The lowest significant dose (LSDs) and IC50 Doses: of methotrexate (MTX), 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FLU) which reduced ATP levels and increased caspase 3 activity (CASP 3) when compared to the vehicle control (P≤0.05) in two lymphoid (Jurkat and CCRF-CEM) and two myeloid (THP1 and KG-1a) leukemia cell lines; and two non-tumor control hematopoietic stem cells (CD34+ HSCs and CD133+ HSCs). The LSDs for ATP levels where used in subsequent investigation of combination treatments on cell-cycle progression, ATP and glutathione levels and DNA damage. The LSDs for caspase 3 activity were used for further investigation of apoptosis.
| Cell Type | Doses | MTX | 6-MP | 5-FLU | ||||
|---|---|---|---|---|---|---|---|---|
| ATP | CASP 3 | ATP | CASP 3 | ATP | CASP 3 | |||
| Lymphoid Cells | Jurkat | LSD | 0.01μM | 0.01μM | 0.01μM | 0.01μM | 0.01μM | 0.01μM |
| IC50 | >50 μM | >50 μM | 2 μM | >50 μM | 30 μM | >50 μM | ||
| CCRF-CEM | LSD | 0.4μM | 2μM | 0.01μM | 0.4μM | 2μM | 10μM | |
| IC50 | >50 μM | >50 μM | 6 μM | >50 μM | >50 μM | >50 μM | ||
| Myeloid Cells | THP1 | LSD | 0.01μM | 0.01μM | 0.01μM | 2μM | 0.01μM | 0.4μM |
| IC50 | >50 μM | >50 μM | 10 μM | >50 μM | >50 μM | >50 μM | ||
| KG1a | LSD | 0.4 μM | 0.4 μM | 50μM | 50μM | 0.4μM | 2μM | |
| IC50 | >50 μM | >50 μM | >50 μM | >50 μM | >50 μM | >50 μM | ||
| Non-Tumor Control Cells | CD34+ HSCs | LSD | 0.4 μM | 0.4 μM | 0.4 μM | 2μM | 0.01μM | 0.4μM |
| IC50 | >50 μM | >50 μM | 50 μM | >50 μM | >50 μM | >50 μM | ||
| CD133+ HSCs | LSD | 0.4 μM | 2 μM | 2μM | 0.4 μM | 0.4 μM | 0.4μM | |
| IC50 | >50 μM | >50 μM | >50 μM | >50 μM | >50 μM | >50 μM | ||