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Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways

Cited 78 time in Web of Science Cited 82 time in Scopus
Authors
Chun, Jaemoo; Kim, Yeong Shik
Issue Date
2013-10-05
Publisher
Elsevier Ireland Ltd
Citation
Chemico-Biological Interactions Vol.205 No.3, pp. 212-221
Keywords
의약학Platycodin DInvasionMMP-9EGFRMAPKAkt
Abstract
Platycodin D (PD), an active triterpenoid saponin from Platycodon grandiflorum, has been known to inhibit the proliferation of a variety of cancer cells, but the effect of PD on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PD inhibits the migratory and invasive abilities of the highly metastatic MDA-MB-231 breast cancer cell line. We demonstrated that a non-cytotoxic concentration of PD markedly suppressed wound healing migration, invasion through the matrigel, and adhesion to an ECM-coated substrate in a dose-dependent manner. Moreover, PD inhibited cell invasion by reducing matrix metalloproteinase (MMP)-9 enzyme activity and mRNA expression. Western blot analysis indicated that PD potently suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) as well as blocked the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. Furthermore, PD treatment inhibited the DNA binding activity of NF-κB, which is known to mediate the expression of epidermal growth factor receptor (EGFR), as observed by electrophoretic mobility shift assay. Specific mechanisms of action exerted by PD involved the downregulation of EGFR and the inhibition of EGF-induced activation of the EGFR, MAPK, and PI3K/Akt pathways. The in vivo studies showed that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in BALB/c nude mice. These results suggest that PD might be a potential therapeutic candidate for the treatment of breast cancer metastasis.
ISSN
0009-2797
Language
English
URI
https://hdl.handle.net/10371/91117
DOI
https://doi.org/10.1016/j.cbi.2013.07.002
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College of Pharmacy (약학대학)Dept. of Manufacturing Pharmacy (제약학과)Journal Papers (저널논문_제약학과)
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