title: Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression.
abstract: Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer.
authors: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Hiroki
authors: H
authors: Fukuda
authors: Department of Pharmacognosy, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Seikou
authors: S
authors: Nakamura
authors: Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Yugo
authors: Y
authors: Chisaki
authors: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Tetsuya
authors: T
authors: Takada
authors: Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Toda
authors: Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Orthopedic Surgery, Matsushita Memorial Hospital, Osaka, Japan.
authors: Hiroaki
authors: H
authors: Murata
authors: Department of Biology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Kazuyuki
authors: K
authors: Itoh
authors: Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Yoshitaka
authors: Y
authors: Yano
authors: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors: Kazuyuki
authors: K
authors: Takata
authors: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: ash@mb.kyoto-phu.ac.jp.
authors: Eishi
authors: E
authors: Ashihara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D051379:Mice; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D014468:Umbelliferones / Q000008:administration & dosage*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C581598:Cdc42 protein, mouse; D014468:Umbelliferones; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; C039952:daphnetin
keywords: Filopodia; LM8; Metastasis; Rho family small GTP-binding proteins; Stress fiber; daphnetin