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Euphohelioscopin A Is a PKC Activator Capable of Inducing Macrophage Differentiation

2012; Elsevier BV; Volume: 19; Issue: 8 Linguagem: Inglês

10.1016/j.chembiol.2012.06.010

1879-1301

Lorenzo de Lichtervelde, Corina E. Antal, Anthony E. Boitano, Ying Wang, Philipp Krastel, Frank Petersen, Alexandra C. Newton, Michael P. Cooke, Peter G. Schultz,

Phytochemistry and biological activities of Ficus species

To identify small molecules that selectively control hematopoietic stem cell differentiation, we performed an unbiased screen using primary human CD34+ cells. We identified a plant-derived natural product, euphohelioscopin A, capable of selectively differentiating CD34+ cells down the granulocyte/monocytic lineage. Euphohelioscopin A also inhibits proliferation and induces differentiation of the myeloid leukemia cell lines THP-1 and HL-60. Mechanistic studies revealed that euphohelioscopin A is an activator of protein kinase C (PKC), and that the promonocytic effects of this natural product are mediated by PKC activation. In addition to shedding insights into normal hematopoiesis, this work may ultimately facilitate the application of stem cell therapies to a host of myeloid dysfunctions.