Additive apoptotic effect of STI571 with the cytoprotective agent amifostine in K-562 cell line

Abstract

Purpose: To study the apoptotic effect of the 2-phenylaminopyrimidine derivative STI571 in combination with antioxidant agents on K-562 cell line derived from a Philadelphia chromosome-positive chronic myeloid leukemia patient. Materials and methods: K-562 (BCR/ABL+), U-937, and HL60 (BCR/ABL-) leukemic cell lines were incubated with STI571 and the antioxidant agents catalase, glutathione, superoxide dismutase, and amifostine (AMI). Apoptotic effect was analyzed by morphological and flow cytometric criteria. Results: STI571 at concentrations higher than 0.25 μmol L-1 produced apoptosis (P<0.05) in K-562 cells only after treatment for 72 h. At the mentioned concentrations, STI571 also induced an increase in the loss of mitochondrial transmembrane potential from 24.6 to 40%. Combination of STI571 (0.5 μmol L-1) with antioxidant agents showed that the cytoprotective agent AMI (0.75 mg mL-1) produced an additive effect in the proapoptotic activity of STI571 in K-562 cells at nuclear (58.8%±2.0 vs. 28.9%±3.3) and mitochondrial (53.3%±3.6 vs. 29.5%±1.2) levels. Conclusions: Our results show that only AMI in combination with STI571, at submicromolar concentration, has an additive effect in K-562 cell line, and it does not have severe toxic effects on Philadelphia chromosome negative cells. © Springer-Verlag 2005.