Apoptosis Deregulation Influences Chemoresistance to Azaguanine in Human Leukemic Cell Lines

Abstract

The involvement of apoptosis in the cytotoxicity mediated by nucleoside analogues, namely azaguanine, and its implication in resistance are not well understood. Using human T-cell acute lymphoblastic leukemia cell lines, sensitive (CEM cells) and resistant to azaguanine (CM3 cells), we observe a decrease in the expression of proapoptotic proteins in CM3 cells, which may be related to the resistance to cell death induced by azaguanine. On the other hand, CM3 cells lack cross resistance with other anticarcinogenic drugs, suggesting that azaguanine may be used alternatively in the presence of chemoresistance. A better knowledge of the apoptotic pathways involved in leukemic cell death resistance may contribute to the development of therapeutic strategies, aimed to prevent chemotherapy resistance.

Keywords: :

• Azaguanine cytotoxicity
• Oxidative stress
• Apoptosis/necrosis
• Lymphoid leukemia
• Chemoresistance

ACKNOWLEDGMENTS

This work is supported in part by a grant-in-aid from the Ministry of Education of Portugal and by Biochemistry Institute of Faculty of Medicine, University of Coimbra, Coimbra, Portugal.