Repositioning antimalarial drugs as anticancer agents: focus on Tafenoquine

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD₅₀ = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD₅₀ = 15.2 μM in HCT116 cells) Further, Tafenoquine induces apoptosis and increases the expression of genes involved in cell cycle arrest and cell death. We also show that cells are sensitized to the apoptotic effects of Tafenoquine following depletion of the heme oxygenase 1 (HMOX-1) gene. Collectively, our studies confirm that antimalarial compounds hold the potential for use as anticancer agents and provide the first evidence to detail the potent efficacy of Tafenoquine against cancer cells in culture.