Fluoxetine increases extracellular levels of 3-methoxy-4-hydroxyphenylglycol in cultured COLO320 DM cells

Abstract

Fluoxetine (Prozac) is a serotonin reuptake inhibitor. It increases extracellular levels of serotonin and is used in relieving the depressive symptoms of cancer patients. It has been reported that the drug may enhance the growth of certain cancer cells. This study investigates whether fluoxetine enhances the growth of a human colon cancer cell line (COLO320 DM) and if it affects the extracellular levels of serotonin or its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) and other monoamines and metabolites at two cell densities. The extracellular levels of serotonin, 5-HIAA and other monoamines and metabolites were measured simultaneously by high performance liquid chromatography from cell-culture media after incubation of cells both with and without fluoxetine for 3 days. The viability of COLO320 DM cells was evaluated using 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). At low cell densities (1.25×10⁵ cells ml⁻¹), fluoxetine at 1–10 μM significantly increased the extracellular levels of serotonin (p < 0.005), 5-HIAA (p < 0.005), and 3-methoxy-4-hydroxyphenylglycol (MHPG; p < 0.001) as compared to the controls. Fluoxetine at 10–100 μM significantly inhibited the growth of COLO320 DM (p < 0.005). At high cell densities (2×10⁶ cells ml⁻¹), fluoxetine at 1–10 μM significantly increased the extracellular levels of MHPG (p < 0.01), and at 10 μM it significantly increased the extracellular levels of 5-HIAA (p < 0.05). Fluoxetine at 100 μM significantly inhibited the growth of the cells (p < 0.0001). These results suggest that fluoxetine at 1 μM of effective concentration may increase the extracellular levels MHPG, in addition to serotonin and 5-HIAA levels, yet not inhibit the growth of COLO320 DM. Copyright © 2004 John Wiley & Sons, Ltd.