CYTOSTATIC ACTIVITY OF TRICYCLIC ANTIDEPRESSANTS AS MEASURED BY A TETRAZOLIUM-BASED COLORIMETRIC ASSAY

Background - Tricyclic antidepressants are frequently used in the supportive care of cancer patients to improve the efficacy of analgesics. Several observations point to the possibility of a direct antitumor activity of these drugs. We report here our studies of three frequently used antidepressants on the growth of a human cancer cell line. Methods - The antiproliferative effect of clomipramine, imipramine, and maprotiline were tested on a renal cancer cell line. Growth inhibition of these cancer cells was judged by a tetrazolium-based assay (MTT). Results - Clomipramine and maprotiline showed antitumor activity after only 2h of drug-cell contact and more pronounced after 24 to 72h of cell exposure to these drugs. Imipramine not show such activity. Growth inhibition was observed at concentrations which can easily be reached by instillation into malignant effusions. Conclusions - The demonstration of a cytostatic effect of clomipramine and maprotiline in vitro should lead to a careful clinical recording of these drugs during cancer chemotherapy. Despite a 5-fold in vitro plasma concentration difference local concentrations in the tumor may be far above the plasma levels. Clomipramine and maprotiline may be used in treatments of malignant effusions where 100 times the concentration active in vitro can be reached.