Activation of PKC-epsilon counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members
Gonelli, A.; Milani, D.; Rimondi, E.; Voltan, R.; Grill, V.; Celeghini, C.
European Journal of Histochemistry Ejh 53(3): 177-182
2009
ISSN/ISBN: 1121-760X PMID: 19864212 Document Number: 634756
Protein kinase C (PKC)-epsilon, 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-epsilon with specific small molecule activator or inhibitor peptides. PKC-epsilon inhibitor and activator peptides showed modest effects on HL-60 maturation when added alone, but PKC-epsilon activator peptide significantly counteracted the pro-maturative activity of tumor necrosis factor (TNF)-alpha towards the monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression and morphological analyses. Moreover, while PKC-epsilon inhibitor peptide showed a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis, PKC-epsilon activator peptide potently counteracted the pro-apoptotic activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic activities of PKC-epsilon envision a potentially important proleukemic role of this PKC family member.