Activation of protein kinase C for protection of cells against apoptosis induced by the immunosuppressor prodigiosin

Prodigiosin (PG) is a red pigment produced by Serratia marcescens with immunosuppressive activity. We had recently shown that PG-induced apoptosis in several cancer cell lines including Jurkat-T cells, while acting rapidly, potently and with no marked toxicity in non-malignant cells. Here we examine the role of protein kinase C (PKC) in the regulation of apoptosis triggered by PG. We evaluated the use of phorbol-myristate acetate (PMA) in the inhibition of apoptosis induced by PG in Jurkat-T cells by using FACS analysis of the phosphatidylserine externalisation, Hoechst 33342 staining and fragmentation pattern of DNA as well as proteolysis of poly-(ADP) ribose polymerase (PARP). The anti-apoptotic effect of PMA was accompanied by phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with MEK inhibitor PD98059 inhibited PMA-induced phosphorylation of ERK1/2 and the cytoprotective ability of PMA, These results suggest that activation of PKC in Jurkat-T cells confer protection against apoptosis induced by PG and that ERK1/2 mediate anti-apoptotic PKC signaling. (C) 2002 Elsevier Science Inc. All rights reserved.