Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

被引:38
作者
Fukuda, Hiroki [1 ]
Nakamura, Seikou [2 ]
Chisaki, Yugo [3 ]
Takada, Tetsuya [1 ]
Toda, Yuki [4 ]
Murata, Hiroaki [5 ,6 ]
Itoh, Kazuyuki [7 ]
Yano, Yoshitaka [3 ]
Takata, Kazuyuki [1 ]
Ashihara, Eishi [1 ]
机构
[1] Kyoto Pharmaceut Univ, Dept Clin & Translat Physiol, Kyoto 607, Japan
[2] Kyoto Pharmaceut Univ, Dept Pharmacognosy, Kyoto 607, Japan
[3] Kyoto Pharmaceut Univ, Educ & Res Ctr Clin Pharm, Kyoto 607, Japan
[4] Kyoto Pharmaceut Univ, Dept Med Chem, Kyoto 607, Japan
[5] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Orthoped, Kyoto, Japan
[6] Matsushita Mem Hosp, Dept Orthoped Surg, Osaka, Japan
[7] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Biol, Osaka, Japan
关键词
LM8; Metastasis; daphnetin; Rho family small GTP-binding proteins; Stress fiber; Filopodia; SMALL INTERFERING RNA; ACTIN STRESS FIBERS; COUMARIN DERIVATIVES; PROTEIN-KINASE; TUMOR-CELLS; GROWTH; DIFFERENTIATION; METASTASIS; ESCULETIN; ARTHRITIS;
D O I
10.1016/j.bbrc.2016.01.179
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:63 / 67
页数:5
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