In vitro and in vivo antitumor activity of YoshixolTR against murine L1210 leukemic cells.
In this report, antiproliferative effects of YoshixolTR in vitro and in vivo were investigated in murine L1210 cells. A proliferation of L1210 cells in vitro was inhibited by YoshixolTR in a dose- and time-dependent manner. This inhibition showed an arrest at the G0/G1 stage of the cell cycle, followed by a flow cytometric measurement. YoshixolTR induced apoptosis-like cell death identified by histological observations (scanning electron and transmission electron microscopy), DNA fragmentation, and a smaller increase in lactate dehydrogenase (LDH). In the in vivo experiments, YoshixolTR (5 microl/kg of body weight, on days 1, 3, and 5) was injected intraperitoneally in mice inoculated with L1210 cells. No marked prolongation of survival occurred between the control group and treated group. However, a survival curve in the treated group showed a shift toward a possible longer survival time. Additionally, on the basis of apoptosis-like cell death due to YoshixolTR as indicated above, a possibility of immunotherapy as a tumor vaccine has been examined. A vaccination of rabbit anti-serum, which consisted of components from the L1210 cells killed by YoshixolTR, produced a dramatic improvement of viability in the leukemic mice. In conclusion, YoshixolTR has an anti-leukemic potency with a new biological mechanism and an inductive potency of super-antigens as immunotherapeutic agents against malignant tumors.
Tanaka
S
S
Shinshu University School of Medicine, Department of Physiology, Nagano, Japan.
Koyama
S
S
Haniu
H
H
Yamaguchi
Y
Y
Motoyoshiya
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D003512:Cyclohexanones / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D011817:Rabbits
D000970:Antineoplastic Agents; D003512:Cyclohexanones; C107152:Yoshixol