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

Gulnihal Kulaksiz-Erkmen, Ozlem Dalmizrak, Gamze Dincsoy-Tuna, Arın Dogan, I Hamdi Ogus, Nazmi Ozer

Department of Biochemistry, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.

Journal of enzyme inhibition and medicinal chemistry 2013 Feb

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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 IC(50) 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.

Citation

Gulnihal Kulaksiz-Erkmen, Ozlem Dalmizrak, Gamze Dincsoy-Tuna, Arın Dogan, I Hamdi Ogus, Nazmi Ozer. Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α). Journal of enzyme inhibition and medicinal chemistry. 2013 Feb;28(1):131-6