A tricyclic anti-depressant, amitriptyline, is a highly prescribed drug for cancer patients for mood elevation but there are limited studies about the interaction of amitriptyline with glutathione S-transferases pi (GST-pi) and glutathione S-transferases alpha (GST-alpha). GST isozymes have been implicated in chemotherapeutic drug resistance. We demonstrated that the concentration dependent inhibition of GST-pi and GST-alpha by amitriptyline followed inverse hyperbolic inhibition curves with IC50 values of 5.54 and 8.32 mM, respectively.

When the varied substrate was GSH, amitriptyline inhibited both isozymes competitively and similar K-i values were found for GST-pi (K-i = 1.61 +/- 0.17 mM) and GST-alpha (K-i = 1.45 +/- 0.20 mM). On the other hand, when the varied substrate was CDNB, the inhibition types were non-competitive for GST-pi (K-i = 1.98 +/- 0.31 mM) and competitive for GST-alpha (K-i = 1.57 +/- 0.16 mM).

Amitriptyline, in addition to its antidepressant effect, might also have a minor supportive role on the effectiveness of the anticancer drugs by decreasing their elimination through inhibiting GST-pi and GST-alpha.