Human T cell leukemia cell death by apoptosis-inducing nucleosides from CD57(+) HLA-DR(bright) natural suppressor cell line.

Abstract

Apoptosis‐inducing nucleosides (AINs) released from CD57+HLA‐DRbright natural suppressor (57.DR‐NS) cell line, derived from human decidual tissue, were isolated from 57.DR‐NS cell culture supernatant by the combination of thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC). Apoptotic cell death was strongly induced in human T cell leukemia Molt4 cells treated with AINs, absolutely depending on DNA strand breaks, with activation of the caspase cascade, especially caspase‐3. The administration of AINs to Molt4 tumor‐bearing severe combined immunodeficiency (SCID) mice resulted in drastic suppression of tumor growth, with a decrease of tumor size and the appearance of apoptotic signals in tumor tissue. Thus, AINs are candidates for development as anticancer agents.