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

VELLÓN L, GONZÁLEZ CID M, DE CAMPOS NEBEL, LARRIPA

CANCER CHEMOTHERAPY AND PHARMACOLOGY

Springer

Año: 2005 vol. 55 p. 602 - 608

0344-5704

AbstractPurpose To study the apoptotic effect of the 2-phenylaminopyrimidine derivative STI571 incombination with antioxidant agents on K-562 cell line derived from a Philadelphiachromosome-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 ìmol 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 ìmol 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 submicromolarconcentration, has an additive effect in K-562 cell line, and it does not have severe toxic effectson Philadelphia chromosome negative cells.