PLAG alleviates chemotherapy-induced thrombocytopenia via promotion of megakaryocyte/erythrocyte progenitor differentiation in mice

Abstract

Previously, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) was reported to have an effect on the proliferation of hematopoietic stem cells (HSCs) or to contribute to the prevention of chemotherapy-induced neutropenia. In this study, we examined the role of PLAG in the differentiation of bone marrow cells from HSCs into progenitor cells in mice. After 15 days, the lineage-negative cells, especially megakaryocyte/erythrocyte progenitors (MEP), were significantly increased in mice that received daily PLAG administration compared to those in the untreated mice. Furthermore, we explored the possibility that the PLAG-induced increase in MEP will contribute to reduction of chemotherapy-induced thrombocytopenia (CIT) in a thrombocytopenia mouse model. Mice were administrated 5-fluorouracil (5-FU) and PLAG. After 7 days, bone marrow cells were analyzed. Treatment with 5-FU powerfully decreased myeloid precursor populations and treatment with 5-FU/PLAG resulted in reduction of decreased myeloid progenitor cell numbers. In addition, numbers of circulating platelets were also increased by PLAG treatment. Taken together, PLAG plays a role in differentiating HSCs toward MEP and alleviating chemotherapy-induced bone marrow cell reduction. Thus PLAG shows its potential to augment the therapeutic effect of anti-cancer drugs-induced thrombocytopenia. ⓒ 2017 Elsevier Ltd