Casticin Promotes Immune Responses, Enhances Macrophage and NK Cell Activities, and Increases Survival Rates of Leukemia BALB/c Mice

Abstract

Casticin, derived from Fructus Viticis, has anticancer properties in many human cancer cells, however, there is no report to show that casticin promotes immune responses and affects the survival rate of leukemia mice in vivo. The aim of this study is to evaluate the effects of casticin on immune responses and the survival rate of WEHI-3 cells generated in leukemia mice in vivo. Animals were divided into six groups: normal control mice, leukemia control mice, mice treated with ATRA (all-trans retinoic acid), and casticin (0.1, 0.2, and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg) treated mice. All animals were treated for 14 days and then measured for body weights, total survival rate, cell markers, the weights of liver and spleen, phagocytosis of spleen cells, NK cell activities and cell proliferation. Results show that casticin did not affect animal appearances, however, it increased body weights and decreased the weights of liver at 0.2 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg treatment. Casticin also decreased spleen weight at 0.2 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg treatment, increased CD3 at 0.1, 0.2 and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg doses and increased CD19 at 0.2 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg treatment but decreased CD11b and Mac-3 at 0.1, 0.2 and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg treatment. Casticin (0.1, 0.2 and 0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg) increased macrophage phagocytosis from PBMC (peripheral blood mononuclear cell) and peritoneal cavity. Furthermore, casticin increased NK cells' cytotoxic activity and promoted T cell proliferation at 0.1-0.4 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math> mg/kg treatment with or without concanavalin A (Con A) stimulation, but only increased B cell proliferation at 0.1 mg/kg treatment. Based on these observations, casticin could be used as promoted immune responses in leukemia mice in vivo.