The effect of some antineoplastic agents on glutathione S-transferase from human erythrocytes

ERAT M., Sakiroglu H.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.28, sa.4, ss.711-716, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 4
  • Basım Tarihi: 2013
  • Doi Numarası: 10.3109/14756366.2012.677837
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.711-716
  • Anahtar Kelimeler: Glutathione S-transferase, inhibition, paclitaxel, cyclophosphamide, gemcitabine, ANTICANCER DRUG-RESISTANCE, MULTIDRUG-RESISTANCE, BREAST-CANCER, INHIBITORS, EXPRESSION, ENZYMES, GST, IDENTIFICATION, MODULATION, PROTEIN
  • Atatürk Üniversitesi Adresli: Evet

Özet

Glutathione S-transferase was purified from human erythrocytes and effects of some antineoplastic agents were investigated on the enzyme activity. The purification procedure was composed of Glutathione-Agarose affinity chromatography after preparation of erythrocytes hemolysate. Using this procedure, the enzyme, having the specific activity of 16.00 EU/mg proteins, was purified 1143-fold with a yield of 80%. The purified enzyme showed a single band on the SDS-PAGE. The effects of paclitaxel, cyclophosphamide, and gemcitabine, are antineoplastic agents, were examined on the in vitro enzyme activity of glutathione S-transferase and were determined to be inhibitors for the enzyme. IC50 values were 0.23 mM for paclitaxel, 5.57 mm for cyclophosphamide, and 6.35 mM for gemcitabine. These constants were 0.182 +/- 0.028 mM and 0.162 +/- 0.062 mM for paclitaxel, 6.97 +/- 0.49 mM and 10.50 +/- 5.43 mM for cyclophosphamide, and 6.71 mM and 7.93 mM for gemcitabine, with GSH and CDNB substrates, respectively. Inhibition types of all inhibitors were noncompetitive.