title: Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α).
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 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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.
authors.forename: Gulnihal
authors.initials: G
authors.lastname: Kulaksiz-Erkmen
authors.forename: Ozlem
authors.initials: O
authors.lastname: Dalmizrak
authors.forename: Gamze
authors.initials: G
authors.lastname: Dincsoy-Tuna
authors.forename: Arın
authors.initials: A
authors.lastname: Dogan
authors.forename: I Hamdi
authors.initials: IH
authors.lastname: Ogus
authors.forename: Nazmi
authors.initials: N
authors.lastname: Ozer
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007421:Intestine, Small / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D000639:Amitriptyline; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D005978:Glutathione