Abstract: The selective serotonin reuptake inhibitor fluoxetine, tricyclic antidepressants amitriptyline and doxepin, and selective norepinephrine reuptake inhibitor mianserin are currently commonly used antidepressants. However, the non-target toxicity of these drugs is unclear. The cytotoxicity of fluoxetine, amitriptyline, mianserin, and doxepin were tested using SKBR3 and MCF-7 human breast cancer cell lines. Biological effects end-points included cell proliferation, intracellular reactive oxygen species (ROS), calcium ion (Ca2+) concentration changes, and DNA damage. Exposure to 0.001∼10 µmol fluoxetine for 24 h significantly increased viability of SKBR3 cells. Cell viability was significantly inhibited when the concentrations of fluoxetine, amitriptyline, and mianserin were higher than 10 µmol/L. Exposure to low concentrations of fluoxetine and amitriptyline for 24 h significantly increased intracellular ROS levels, while mianserin and doxepin exposure for 3 h significantly elevated intracellular ROS levels. Concentrations of 0.001∼10 µmol/L of the four antidepressants for 24 h had no significant influence on intracellular Ca2+ concentra-tion change, but concentrations higher than 10 µmol/L significantly increased intracellular Ca2+ levels. The comet assay showed that 0.1 and 1 µmol/L fluoxetine slightly induced DNA damage in SKBR3 cells. Cytotoxicity of fluoxetine and amitriptyline was also exam-ined in MCF-7 cells. The evaluated biological effect endpoints including cell proliferation, and intracellular ROS and Ca2+ concentration changes. Similar to SKBR3 cells, only fluoxetine promoted the proliferation of MCF-7 cells at low concentrations. At higher exposure concentrations, fluoxetine and amitriptyline significantly increased intracellular Ca2+ levels. However, fluoxetine and amitriptyline only significant increased intracellular ROS levels at higher exposure concentrations of 25 and 50 µmol/L, which differed from the observation that they can induce ROS generation in SKBR3 cells at low concentrations. These results provide basic experimental data to evaluate the non-target toxicity of these antidepressants.

Key words: antidepressant, breast cancer cell, cell proliferation, reactive oxygen species (ROS), DNA damage