Studies of the anticancer effect of calcineurin B.
Calcineurin (CN) is a Ca (2+)/calmodulin-stimulated protein phosphatase. It is a heterodimeric enzyme consisting of a catalytic subunit (CN A) and a Ca2+ -binding regulatory subunit (CN B), which plays an important role in the human immune system. Its regulatory subunit, CN B, on its own, was found to have a remarkable anticancer effect in mice. To clarify the basis of this action the in vivo and in vitro effect of CN B on several types of mice immunocytes was investigated. The phagocytic activity of peritoneal macrophages of both normal mice and mice bearing S 180 solid tumors increased when CN B was injected daily. In vitro examination using a modified MTT assay and an [3H] incorporation assay showed that the cytotoxicity of peritoneal macrophages was increased substantially. CN B also increased the natural killer activity of murine spleen lymphocytes in vivo and in vitro, and synergized with concanavalin A in stimulating their proliferation. Our results indicate that CN B has a significant stimulatory action on the immune system that may partially account for its anticancer activity.
Jin
Feng Z
FZ
Department of Biochemistry and Molecular Biology, Beijing Key Laboratory, Beijing Normal University, Beijing, PR China.
Lian
Mu L
ML
Wang
Xia
X
Wei
Qun
Q
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019703:Calcineurin / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D012510:Sarcoma 180 / Q000188:drug therapy / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D003208:Concanavalin A; D019703:Calcineurin