title: YoshixolTR inhibits B16 melanoma cell growth in vivo and induces apoptosis-like (quantum thermodynamic) cell death.
abstract: In this report, antitumor effects of YoshixolTR in vivo and in vitro were investigated in B16 melanoma cells. For in vivo experiments, the present study shows a dramatic inhibition of tumor growth of B16 melanoma transplanted on the leg or intraperitoneal cavity after treatment with YoshixolTR intraperitoneally. A proliferation of B16 cells in vitro was inhibited by YoshixolTR in a dose-and time-dependent manner. YoshixolTR induced apoptosis-like cell death in histological observations (phase-contrast, scanning and transmission electron microscopy), DNA fragmentation, and a smaller increase in lactate dehydrogenase (LDH) as a marker of cell leakage. Immunohistochemical investigation of cytoskeletal components, such as actin and tubulin, showed a cell wall disruption of B16 melanoma cells and a nuclear extrusion after the treatment with YoshixolTR. Treatment with YoshixolTR in vitro showed an arrest at the G0/G1 stage of the cell cycle, followed by a flow cytometric measurement. As a possible physiological mechanism of YoshixolTR on B16 melanoma cells, intracellular Ca++ was measured with Fura-2 technique. An adequate concentration of YoshixolTR, which induces apoptosis-like cell death, showed a decrease in intracellular free Ca++ concentration. In conclusion, YoshixolTR has an antitumor potency with a new biological mechanism of cell growth, proliferation, and differentiation, including cellular signalling pathways, and is a new candidate for an ideal chemotherapeutic agent against malignant tumors.
authors.affiliation: Shinshu University School of Medicine, Department of Physiology, Nagano, Japan. skoyama@gipac.shinshu-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Koyama
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Haniu
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: J
authors.initials: J
authors.lastname: Motoyoshiya
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D003512:Cyclohexanones / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; D004273:DNA, Neoplasm; C107152:Yoshixol; D002118:Calcium