Rhapontigenin suppresses cell migration and invasion by inhibiting the PI3K-dependent Rac1 signaling pathway in MDA-MB-231 human breast cancer cells.
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| Abstract |
The invasive behavior of cancer cells resulting in metastasis is the major cause of cancer-related deaths. Rhapontigenin (1) has various biological activities including anticancer activities. However, whether and how 1 affects cancer invasion has never been explored. Here, we examined the anti-invasive effects of 1 and its underlying molecular mechanisms in the highly invasive human breast cancer cell line designated MDA-MB-231. At noncytotoxic concentrations, 1 strongly suppressed serum-induced cell migration and invasion as judged by Boyden chamber analysis and wound-healing assays, respectively. Compound 1 strikingly reduced Rac1 activity as judged by both absorbance-based and pull-down assays. In addition, its downstream effectors such as WASP-family verprolin homologous proteins 2 (WAVE-2) and p21-activated kinase 1 (PAK1) signaling cascades were attenuated after treatment with 1. Immunofluorescence staining showed that 1 diminished lamellipodia formation at the leading edge of cells. Finally, 1 decreased the phosphorylation of phosphoinisitide-3-kinase (PI3K) and AKT. Rac1 activity was inhibited by the PI3K inhibitor wortmannin. Taken together, these results suggest that 1 suppresses breast cancer cell migration and invasion, which is involved in inhibiting the PI3K-dependent Rac1 signaling pathway.
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| Authors | Ji Sung Kim, Chi Gu Kang, Sung-Hoon Kim, Eun-Ok Lee |
| Journal | Journal of natural products (J Nat Prod) Vol. 77 Issue 5 Pg. 1135-9 (May 23 2014) ISSN: 1520-6025 [Electronic] United States |
| PMID | 24828286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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