title: Tetracycline derivative minocycline inhibits autophagy and inflammation in concanavalin-a-activated human hepatoma cells.
abstract: Inhibition of soluble matrix metalloproteinase (MMP) activity is among the non-antibiotic cellular effects exerted by the anti-inflammatory tetracycline derivative minocycline. The impact of minocycline on the signal transduction functions of membrane-bound MMPs is however unknown. We assessed minocycline in a concanavalin-A (ConA)-activated human HepG2 hepatoma cell model, a condition known to increase the expression of membrane type-1 MMP (MT-MMP) and to trigger inflammatory and autophagy processes. We found that minocycline inhibited ConA-induced formation of autophagic acidic vacuoles, green fluorescent microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta formation, gene and protein expression of autophagy biomarker BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), invasion biomarker MT1-MMP, and inflammation biomarker cyclooxygenase (COX)-2. Gene silencing of MT1-MMP abrogated ConA-induced formation of autophagic acidic vacuoles and ConA-induced expressions of BNIP3 and COX-2. Minocycline was also shown to inhibit ConA-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation as well as gene expression of NANOS1, a biomarker believed to colocalize with MT1-MMP and the specific silencing of which further inhibited ConA-induced STAT3 phosphorylation. Collectively, our data demonstrate that part of minocycline's effects on autophagy could be exerted through the inhibition of MT1-MMP signaling functions, which contribute to the autophagy and inflammatory phenotype of ConA-activated HepG2 cells.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Québec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Desjarlais
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Québec, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pratt
authors.affiliation: Département des Sciences Biologiques, Centre de Recherche BioMed, Université du Québec à Montréal, Quebec, Canada.
authors.forename: Amine
authors.initials: A
authors.lastname: Lounis
authors.affiliation: Département des Sciences Biologiques, Centre de Recherche BioMed, Université du Québec à Montréal, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mounier
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Québec, Canada.
authors.forename: Khadidja
authors.initials: K
authors.lastname: Haidara
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Québec, Canada.
authors.forename: Borhane
authors.initials: B
authors.lastname: Annabi
keywords: antibiotic; autophagy; cancer; concanavalin-A; hepatocellular carcinoma cells; inflammation; minocycline