Rhapontigenin suppresses cell migration and invasion by inhibiting the PI3K-dependent Rac1 signaling pathway in MDA-MB-231 human breast cancer cells.
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.
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University , 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
Ji Sung
JS
Kim
Chi Gu
CG
Kang
Sung-Hoon
SH
Kim
Eun-Ok
EO
Lee
D000730:Androstadienes / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D015394:Molecular Structure; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013267:Stilbenes; C431126:rhapontigenin; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin