Suppression by protein kinase C inhibitors of tumor promoter enhancement of Epstein-Barr virus-induced growth transformation.
The tumor promoter teleocidin activates latent Epstein-Barr virus (EBV) genomes and enhances EBV-induced growth transformation of human B cells, with an activity comparable to that of 12-O-tetradecanoyl-phorbol-13-acetate (TPA). It has been suggested that the TPA induction of EBV genomes is mediated by protein kinase C (PKC), an enzyme closely linked to signal transduction. We examined newly isolated, highly selective PKC inhibitors, UCN-01 (7-hydroxyl-staurosporine) and calphostin C, for the possible suppression of teleocidin enhancement of cord blood B lymphocyte growth transformation by EBV. 0.2 nM teleocidin B4 enhanced EBV-induced 3H-thymidine uptake 6 times, outgrowth in limiting dilution culture 5 times, and colony formation in semisolid agar 3 times. All these events were suppressed by exposure to 10-100 nM UCN-01 or to calphostin C. Our findings suggest that the tumor promoter enhancement of EBV growth transformation is probably mediated by PKC.
Kinoshita
T
T
Department of Virology, Hokkaido University School of Medicine, Sapporo, Japan.
Takahashi
I
I
Kobayashi
E
E
Tamaoki
T
T
Irie
K
K
Koshimizu
K
K
Osato
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000956:Antigens, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology*; D009281:Naphthalenes; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000031:analogs & derivatives
D000470:Alkaloids; D000956:Antigens, Viral; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D008235:Lyngbya Toxins; D009281:Naphthalenes; D011083:Polycyclic Compounds; C022176:teleocidins; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C