Frondoside A has an anti-invasive effect by inhibiting TPA-induced MMP-9 activation via NF-κB and AP-1 signaling in human breast cancer cells

Park,Sun  Young; Kim,Young  Hun; Kim,YoungHee; Lee,Sang-Joon

doi:10.3892/ijo.2012.1518

Frondoside A has an anti-invasive effect by inhibiting TPA-induced MMP-9 activation via NF-κB and AP-1 signaling in human breast cancer cells

Authors:
- Sun Young Park
- Young Hun Kim
- YoungHee Kim
- Sang-Joon Lee
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Affiliations: Bio-IT Fusion Technology Research Institute, Busan 609-735, Republic of Korea, Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea, Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea
Published online on: June 14, 2012 https://doi.org/10.3892/ijo.2012.1518
Pages: 933-940

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Abstract

Metastasis and invasion are among the main causes of death in patients with malignant tumors. The aim of this study was to determine the anti-invasive activity of frondoside A against human breast cancer cells. We investigated the inhibitory effect of frondoside A on cell clonogenicity, invasion and migration in TPA-stimulated human breast cancer cells at non-cytotoxic concentrations. Frondoside A significantly attenuated TPA-induced colony formation, invasion and migration in MBA-MB-231 human breast cancer cells. Induction of MMP-9 is especially important for the metastasis of many cancer tumor cell types. Additionally, we found that frondoside A suppresses TPA-induced MMP-9 enzymatic activity, secretion and expression. This effect was associated with reduced activation of AP-1 and NF-κB, and correlated with enhanced expression of TIMP-1 and TIMP-2. Frondoside A significantly inhibited the TPA-induced MMP-9 expression possibly via the suppression of AP-1 and NF-κB signaling pathways. Frondoside A reduces the activation of the PI3K/Akt, ERK1/2 and p38 MAPK signals. These results suggest that the anti-metastatic effects of frondoside A on human breast cancer cells might result from inhibited TPA activation of AP-1 and NF-κB and reduced TPA activation of PI3K/Akt, ERK1/2 and p38 MAPK signals, ultimately leading to downregulation of MMP-9 expression. These results indicate the role of frondoside A in metastasis and its underlying molecular mechanisms, thus, suggesting frondoside A as a chemopreventive agent for metastatic breast cancer.

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