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

摘要

Abstract 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-π) and glutathione S-transferases alpha (GST-α). GST isozymes have been implicated in chemotherapeutic drug resistance. We demonstrated that the concentration dependent inhibition of GST-π and GST-α 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-π (K_i?=?1.61?±?0.17?mM) and GST-α (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-π (K_i?=?1.98?±?0.31?mM) and competitive for GST-α (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-π and GST-α.