Fluoxetine (ProzacTM) is a commonly used antidepressant drug. It selectively inhibits the reuptake of serotonin in neurons. The imaging agent, 5-iodo-2((2-((dimethylamino)methyl) phenyl)thio)-benzyl alcohol (IDAM), selectively binds to the serotonin transporter (SERT) in the cell membrane. We previously found that fluoxetine inhibited melanoma cell growth and metastastasis in vivo. In vitro the IC50 for fluoxetine is between 14-22 mM. Herein we evaluated the effect of fluoxetine on melanoma cell invasion and IDAM binding in the human melanoma cell lines, A375, Mewo and SB2. We found that all three melanoma cell lines specifically bound 125I labeled IDAM. The maximum binding (Bmax) ranged from 0.74 to 4.99 pmol/100,000 cells and the binding affinity (KD) ranged 10.6 to 38.7 nM. Fuoxetine competed for IDAM binding in the three melanoma cell lines and the IC50 ranged from 160 to 579 nM. Fluoxetine inhibited invasion of A375 melanoma at 1mM, which is ∼10-fold lower than the IC50 for growth inhibition. These data suggest that SERT is involved in inhibition of melanoma invasion. Moreover, the relative low concentration to inhibit melanoma invasion provides a strong rationale for using fluoxetine as part of a treatment regimen for melanoma patients.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]