In vitro and in vivo antiturnor activity of Yoshixol(TR) against murine L1210 leukemic cells

In this report, antiproliferative effects of Yoshixol(TR) in vitro and in v ivo were investigated in murine L1210 cells. A proliferation of L1210 cells in vitro was inhibited by Yoshixol(TR) in a dose- and time-dependent manne r. This inhibition showed an arrest at the G(0)/G(1) stage of the cell cycl e, followed by a flow cytometric measurement. Yoshixol(TR) induced apoptosi s-like cell death identified by histological observations (scanning electro n and transmission electron microscopy), DNA fragmentation, and a smaller i ncrease in lactate dehydrogenase (LDH). In the in vivo experiments, Yoshixo l(TR) (5 mu l/kg of body weight, on days 1, 3, and 5) was injected intraper itoneally in mice inoculated with L1210 cells. No marked prolongation of su rvival occurred between the control group and treated group. However, a sur vival curve in the treated group showed a shift toward a possible longer su rvival time. Additionally, on the basis of apoptosis-like cell death due to Yoshixol(TR) as indicated above, a possibility of immunotherapy as a tumor vaccine has been examined. A vaccination of rabbit anti-serum, which consi sted of components from the L1210 cells killed by Yoshixol(TR), produced a dramatic improvement of viability in the leukemic mice. In conclusion, Yosh ixol(TR) has an antileukemic potency with a new biological mechanism and an inductive potency of super-antigens as immunotherapeutic agents against ma lignant tumors. (C) 1999 Elsevier Science Inc. All rights reserved.