Denbinobin suppresses breast cancer metastasis through the inhibition of Src-mediated signaling pathways
Journal
Journal of Nutritional Biochemistry
Journal Volume
22
Journal Issue
8
Pages
732-740
Date Issued
2011
Author(s)
Abstract
Denbinobin (5-hydroxy-3,7-dimethoxy- 1,4-phenanthraquinone), a biologically active chemical isolated from Ephemerantha lonchophylla, has been demonstrated to display anti-cancer activity. Breast cancer is the leading cause of female mortality, and the high mortality is mainly attributable to metastasis. Src kinase activity is elevated in many human cancers, including breast cancer, and is often associated with aggressive disease. In the present study, we examined the anti-metastatic effects of denbinobin through decreasing Src kinase activity in human and mouse breast cancer cells. Denbinobin caused significant block of Src kinase activity in both human and mouse breast cancer cells. Moreover, phosphorylation of the signaling molecules focal adhesion kinase, Crk-associated substrate and paxillin downstream of Src was also inhibited by denbinobin. Furthermore, denbinobin inhibited the in vitro migration, invasion and in vivo metastasis of breast cancers in a mouse metastatic model. The denbinobin-treated group showed a significant reduction in tumor metastasis, orthrotopic tumor volume, and spleen enlargement compared to the control group. In addition, transfection of breast cancer cells with a plasmid coding for a constitutively active Src prevented the denbinobin-mediated phosphorylation of Src and downstream molecules and cell migration. Our findings provide evidences that denbinobin inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and metastasis, suggesting that it has therapeutic potential in breast cancer treatment. ? 2011 Elsevier Inc.
SDGs
Other Subjects
antineoplastic agent; Crk associated substrate protein; denbinobin; focal adhesion kinase; herbaceous agent; protein kinase; Src kinase; unclassified drug; animal cell; article; breast metastasis; cancer cell; cancer inhibition; cell migration; controlled study; enzyme activity; enzyme phosphorylation; Ephemerantha lonchophylla; human; human cell; in vitro study; medicinal plant; molecular mechanics; mouse; nonhuman; splenomegaly; tumor volume; Animals; Anthraquinones; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Crk-Associated Substrate Protein; Female; Focal Adhesion Kinase 1; Humans; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Paxillin; Phenanthrenes; Phosphorylation; Signal Transduction; src-Family Kinases; Transfection; Ephemerantha lonchophylla
Type
journal article