Anti-Migratory Effects of 4'-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway

Sara Franceschelli; Daniela Maria Pia Gatta; Alessio Ferrone; Giulia Mezza; Lorenza Speranza; Mirko Pesce; Alfredo Grilli; Marialucia Gallorini; Viviana di Giacomo; Barbara Ghinassi; Serena Fiorito; Salvatore Genovese; Emanuela Ricciotti; Mario Felaco; Antonia Patruno

doi:10.3390/antiox9060470

Anti-Migratory Effects of 4'-Geranyloxyferulic Acid on LPS-Stimulated U937 and HCT116 Cells via MMP-9 Down-Regulation: Involvement of ROS/ERK Signaling Pathway

Antioxidants (Basel). 2020 Jun 1;9(6):470. doi: 10.3390/antiox9060470.

Authors

Affiliations

¹ Department of Medicine and Science of Aging, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy.
² Department of Oncology, ASL2, SS Annunziata Hospital, 66100 Chieti-Pescara, Italy.
³ Department of Pharmacy, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy.
⁴ Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy.
⁵ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Matrix metalloproteinases (MMPs) play a crucial role in tumor angiogenesis, and metastasis. 4'-geranyloxyferulic acid (GOFA) has anti-tumor and anti-inflammatory proprieties. Herein, we aimed to determine whether this compound affects cell survival, invasion, and migration through reactive oxygen species (ROS)-mediated MMPs activation of extracellular signal-regulated kinases (ERKs) and p38 signaling in lymphocytic histiocytoma (U937) and colorectal cancer (HCT116) cells. We observed that lipopolysaccharide (LPS) stimulated U937 and HCT116 cells presented abnormal cell proliferation and increased metalloproteinase (MMP-9) activity and expression. Non-cytotoxic doses of GOFA blunted matrix invasive potential by reducing LPS-induced MMP-9 expression and cell migration via inhibiting ROS/ ERK pathway. GOFA also attenuated apoptosis and cell senescence. Our findings indicate that GOFA, inhibiting cancer cell proliferation and migration, could be therapeutically beneficial to prevent tumor metastasis.

Keywords: 4′-geranyloxyferulic acid; ROS; apoptosis; colorectal cancer cells; lymphocytic histiocytoma cells; metalloproteinase; migration; p38; pERK; proliferation; senescence.