Novel vitamin D analogues; cytotoxic and anti-proliferative activity against a diffuse large B-cell lymphoma cell line and B-cells from healthy donors

Calcitriol (1,25-dihydroxyvitamin D-3, 1,25D(3)) and vitamin D side-chain modified analogs (VDAs) have gained considerable attention as potential drugs in the treatment of acute myeloid leukemia (AML), yet studies of the impact of 1,25D(3) and VDAs upon other haematological malignancies are more limited. To address this gap in knowledge, we have examined the action of 1,25D(3) and VDAs on a human cell line (DOHH2, K422) typifying diffuse large B-cell lymphoma (DLBCL) and also peripheral blood B-cells isolated from healthy donors. 1,25D(3) and certain VDAs displayed moderate cytotoxic and pro-apoptotic actions upon DLBCL cells.. 1,25D(3) and VDAs (100 nM) caused the death of approximately 40% DOHH2 cells after 24 h stimulation, similar to their impact on HL-60 cells (acute myeloid leukaemia cell line). In addition, 1,25D(3) and VDAs displayed concentration and time-dependent anti-proliferative actions upon stimulated B-cells from healthy donors. The VDAs inhibited proliferation by approximately 30%. Hence VDAs may offer therapeutic potential for the treatment of DLBCL or conditions benefitted by B-cell depletion. (C) 2015 Elsevier Ltd. All rights reserved.