Prostaglandin E2 induces growth inhibition, apoptosis and differentiation in T and B cell-derived acute lymphoblastic leukemia cell lines (CCRF-CEM and Nalm-6)

Abstract

Despite advances in the treatment of ALL, in most patients long-term survival rates remain unsatisfactory. The objective of the present study was to investigate the anti-cancer effects of Prostaglandin E2 (PGE2) in two different ALL cell lines (CCRF-CEM (T-ALL) and Nalm-6 (B-ALL)). The anti-leukemic effects of PGE2 were also compared with two epigenetic compounds (trichostatin A and 5-aza-2´-deoxycytidine). MTT assay was used to assess growth inhibition by anti-cancer drugs in these cells. All three compounds were shown to induce apoptosis in both ALL cell lines using flow cytometry and Western blotting. To evaluate the differentiation induction by these agents, the expressions of CD19 and CD38 markers on Nalm-6 cell line and CD7 marker on CCRF-CEM cell line were assayed. Surprisingly, the flow cytometric analysis showed a significant increase in CD markers expression in response to PGE2 treatments. We, for the first time, provide evidences that PGE2 has anti-leukemic effects and induces differentiation at micromolar ranges in both T- and B-cell derived ALL cell lines. Since T-ALL cells are insensitive to current chemotherapies, these findings may help the designing of new protocols for T-ALL differentiation therapy in the future.