Activation of PKC-e counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members

Protein kinase C (PKC)-e, a component of the serine/threonine PKC family, has been shown to influence the survival and differentiation pathways of normal hematopoietic cells. Here, we have modulated the activity of PKC-e with specific small molecule activator or inhibitor peptides. PKC-e inhibitor and activator peptides showed modest effects on HL-60 maturation when added alone, but PKC-e activator peptide significantly counteracted the pro-maturative activity of tumor necrosis factor (TNF)-a towards the monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression and morphological analyses. Moreover, while PKC-e inhibitor peptide showed a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis, PKC-e activator peptide potently counteracted the pro-apoptotic activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic activities of PKC-e envision a potentially important proleukemic role of this PKC family member.