PMID- 27573547 OWN - NLM STAT- MEDLINE DCOM- 20170403 LR - 20171116 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 49 IP - 3 DP - 2016 Sep TI - Suppression of MMP-9 and FAK expression by pomolic acid via blocking of NF-kappaB/ERK/mTOR signaling pathways in growth factor-stimulated human breast cancer cells. PG - 1230-40 LID - 10.3892/ijo.2016.3585 [doi] AB - The expression of matrix metalloproteinase-9 (MMP-9) and the phosphorylation of focal adhesion kinase (FAK) have been implicated in the invasion, metastasis and cell motility of cancer cells. It is considered that epidermal growth factor (EGF) may increase cell motility, an event involved in cancer cell invasion and metastasis. Pomolic acid (PA), an active triterpenoid from Euscaphis japonica, is known to inhibit the proliferation of a variety of cancer cells, but the effect of PA on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PA inhibits the migratory and invasive abilities of highly metastatic MDA-MB‑231 cells. Transwell invasion, wound-healing assay and F-actin reorganization showed that PA significantly inhibits the EGF-induced invasion, migration and cell motility by reducing expression of MMP-9 and FAK phosphorylation. In particular, PA potently suppressed the phosphorylation of nuclear factor (NF)-kappaB, extraceullar signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, PA treatment inhibited the DNA binding activity of NF-kappaB and activator protein (AP)-1, which is known to mediate the expression of EGFR and MMP-9. These results suggest that PA may be a potential therapeutic candidate for treatment of breast cancer metastasis. FAU - Park, Ji-Hyun AU - Park JH AD - College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea. FAU - Cho, Yoon Young AU - Cho YY AD - Department of Oncology/Hematology, Daegu Catholic University Medical Center, Daegu 42472, Republic of Korea. FAU - Yoon, Seong Woo AU - Yoon SW AD - Department of Korean Internal Medicine, Korean Medicine Cancer Center, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea. FAU - Park, Byoungduck AU - Park B AD - College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea. LA - eng PT - Journal Article DEP - 20160629 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (NF-kappa B) RN - 60HAB1ZK1T (pomolic acid) RN - 62229-50-9 (Epidermal Growth Factor) RN - 6SMK8R7TGJ (Oleanolic Acid) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.2 (Focal Adhesion Kinase 1) RN - EC 2.7.10.2 (PTK2 protein, human) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Antineoplastic Agents, Phytogenic/*pharmacology MH - Breast Neoplasms/drug therapy/*metabolism MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Epidermal Growth Factor/pharmacology MH - Female MH - Focal Adhesion Kinase 1/*metabolism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - MAP Kinase Signaling System/drug effects MH - Matrix Metalloproteinase 9/*metabolism MH - NF-kappa B/metabolism MH - Neoplasm Invasiveness MH - Oleanolic Acid/*analogs & derivatives/pharmacology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation/drug effects EDAT- 2016/08/31 06:00 MHDA- 2017/04/04 06:00 CRDT- 2016/08/31 06:00 PHST- 2016/04/22 00:00 [received] PHST- 2016/06/14 00:00 [accepted] PHST- 2016/08/31 06:00 [entrez] PHST- 2016/08/31 06:00 [pubmed] PHST- 2017/04/04 06:00 [medline] AID - 10.3892/ijo.2016.3585 [doi] PST - ppublish SO - Int J Oncol. 2016 Sep;49(3):1230-40. doi: 10.3892/ijo.2016.3585. Epub 2016 Jun 29.