Repurposing fluoxetine to treat lymphocytic leukemia: Apoptosis induction, sigma-1 receptor upregulation, inhibition of IL-2 cytokine production, and autophagy induction

Childhood cancer has a cure rate of as low as 15% in low-income countries, suggesting a need for cheaper treatment options. Fluoxetine is a thoroughly safety-tested drug that may target the sigma-1 receptor (σ1-R).
Using the human leukemic cell line, Jurkat, we investigated the effects of fluoxetine on cell survival using XTT and trypan blue staining. Apoptosis was measured using AnnexinV/PI staining and western blot analysis of caspase cleavage. IL-2 secretion of Jurkat cells in response to PHA/PMA was measured using ELISA, and the expression of AKT/pAKT and the σ1-R were measured using western blotting.
Fluoxetine-induced apoptosis and G-2 cell cycle arrest. Fluoxetine reduced IL-2 secretion dose-dependently and could be further potentiated by σ1-R antagonist BD1047 (P < 0.05). Fluoxetine inhibited pAKT six hours post-treatment (P < 0.05). The expression of the σ1-R showed a significant increase between 12 to 48 hours in Jurkat cells (P < 0.05). At the same time, there was a substantial increase in autophagy.
Fluoxetine may have the potential for acute leukemia treatment. Co-treatment with a σ1-R antagonist increases fluoxetine-induced apoptosis, possibly targeting AKT phosphorylation and autophagy activation.