title: Effect of PKC412, a selective inhibitor of protein kinase C, on lung metastasis in mice injected with B16 melanoma cells.
abstract: PKC412, a selective inhibitor of protein kinase C (PKC), is currently in clinical trials as an anti-tumor drug. In the present study, we investigated the anti-metastatic effect of PKC412 using an experimental metastatic mouse model intravenously injected with melanoma cells. One-hour exposure to various concentrations of PKC412 (0.5, 5 and 50 microM) dose-dependently reduced the lung-metastatic potential of highly metastatic B16-F10 and -BL6 mouse melanoma cells in syngeneic mice. Following the exposure, PKC activities in B16-F10 and -BL6 cells were significantly decreased, but growth curves were not influenced. To elucidate the mechanism of the anti-metastatic effect of PKC412, we examined the activity to invade the extracellular matrix and the platelet-aggregating activity of the melanoma cells incubated with PKC412 (0.5, 5 and 50 microM) for 1 hour. PKC412 significantly reduced both the invasive and platelet-aggregating activities. These results suggest that PKC412 shows an anti-metastatic function through the inhibition of the invasive and/or platelet-aggregating activities of melanoma cells. PKC412 is potentially a promising candidate for an anti-metastatic agent.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Satomi
authors.initials: S
authors.lastname: Kagota
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Masaru
authors.initials: M
authors.lastname: Kunitomo
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D019311:Staurosporine; C059539:midostaurin