Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-jt) and alpha (GST-alpha)

摘要

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-tt) and glutathione S-transferases alpha (GST-a). GST isozymes have been implicated in chemotherapeutic drug resistance. We demonstrated that the concentration dependent inhibition of GST-tt and GST-a by amitriptyline followed inverse hyperbolic inhibition curves with /C50 values of 5.54 and 8.32 mM, respectively.When the varied substrate was GSH, amitriptyline inhibited both isozymes competitively and similar K. values were found for GST-tt (K = 1.61 (+-)0.17mM) and GST-a (/C=1.45(+-)0.20mM). On the other hand, when the varied substrate was CDNB, the inhibition types were non-competitive for GST-tt (K. = 1.98(+-)0.31 mM) and competitive for GST-a (K = 1.57(+-)0.16mM).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-tt and GST-alpha.