Article Synopsis
- THC, the active component of cannabis, shows potential as a cytotoxic agent against leukemia cells when combined with traditional anti-leukemia therapies.
- Research indicates that low doses of THC can enhance the effectiveness of these therapies by reducing the necessary concentration (IC(50)) needed to kill cancer cells by about 50%.
- The sensitizing effect of THC is linked to its ability to decrease levels of phosphorylated ERK, suggesting that inhibition of the MAPK/ERK signaling pathway plays a role in this enhanced cell death.
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Article Abstract
Delta(9)-Tetrahydrocannabinol (THC) is the active metabolite of cannabis, which has demonstrable cytotoxic activity in vitro. In support of our previously published data, we have investigated the interactions between THC and anti-leukemia therapies and studied the role of the signalling pathways in mediating these effects. Results showed clear synergistic interactions between THC and the cytotoxic agents in leukemic cells. Additionally, exposure of cells to sub lethal levels of THC (1 microM) sensitised cells to these cytotoxic agents, by reducing IC(50) values by approximately 50%. Sensitisation appeared to be dependent upon the ability of THC to down regulate phosphorylated ERK, as cells dominantly expressive of MEK were not sensitised to the cytotoxic drugs by equi-molar amounts of THC. Overall, these results demonstrate for the first time that a combination approach with THC and established cytotoxic agents may enhance cell death in vitro. Additionally the MAPK/ERK pathway appears responsible in part for these effects.
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