期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 28, 期 1, 页码 131-136出版社
INFORMA HEALTHCARE
DOI: 10.3109/14756366.2011.639017
关键词
Amitriptyline; anticancer drugs; GST-alpha; GST-pi; GSTs
资金
- H.U.B.A.B. [06D061011001]
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.
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