Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 26, Issue 12, Pages 1087-1097Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2022.2166829
Keywords
Acute lymphocytic leukemia; autophagy; cancer; childhood cancer; sigma-1 receptor
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Childhood cancer has a low cure rate in low-income countries, and a cheaper treatment option is needed. Fluoxetine, a well-tested drug, may be effective in treating acute leukemia by targeting the sigma-1 receptor.
BackgroundChildhood 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 (sigma 1-R).Research design and methodsUsing 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 sigma 1-R were measured using western blotting.ResultsFluoxetine-induced apoptosis and G-2 cell cycle arrest. Fluoxetine reduced IL-2 secretion dose-dependently and could be further potentiated by sigma 1-R antagonist BD1047 (P < 0.05). Fluoxetine inhibited pAKT six hours post-treatment (P < 0.05). The expression of the sigma 1-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.ConclusionsFluoxetine may have the potential for acute leukemia treatment. Co-treatment with a sigma 1-R antagonist increases fluoxetine-induced apoptosis, possibly targeting AKT phosphorylation and autophagy activation.
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