Objective: To detect the relationship between sensitivity of malignant hematopoietic cells to arsenic trioxide (As2O3) and cellular capacity against oxidation.
Methods: Nine cell lines derived from hematopoietic malignancies were treated with As2O3 in vitro. Apoptosis was assessed by cellular viability, cytomorphology and flow cytometry. The As2O3-treated cells were examined for glutathione (GSH) level and activity of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione peroxidase (GPX).
Results: Of the 9 cell lines examined, the acute promyelocytic leukemia cell line NB4 and its retinoic acid-resistant subclones R2 and MR2, the Burkitt lymphoma cell line Namalwa and multiple myeloma cell line RPMI 8226 were sensitive to As2O3-induced apoptosis while the acute T cell leukemia cell line (Jurkat) and 3 cell lines (HL-60, U937, K562) of myelogenous leukemia origin were not. In comparison with the sensitive cell lines, higher activity of CAT was found in HL-60 and U937, higher level of GSH in Jurkat, and both in K562. However, activity of GPX, GST and SOD did not significantly correlate with their resistance to As2O3-induced apoptosis.
Conclusion: Intracellular GSH level and/or catalase activity are important factors to determine sensitivity of malignant hematopoietic cells to As2O3-induced apoptosis.