title: Mycobacterium indicus pranii (Mw) inhibits invasion by reducing matrix metalloproteinase (MMP-9) via AKT/ERK-1/2 and PKCα signaling: A potential candidate in melanoma cancer therapy.
abstract: Invasion and metastasis via induction of matrix metalloproteinases are the main causes of death in melanoma cancer. In this study, we investigated the inhibitory effects of heat killed saprophytic bacterium Mycobacterium indicus pranii (Mw) on B16F10 melanoma cell invasion. Mw reported to be an immunomodulator has antitumor activity however, its effect on cancer cell invasion has not been studied. Highly invasive B16F10 melanoma was found sensitive to Mw which downregulated MMP-9 expression. Mw treatment inhibited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) transcriptional activity and respective DNA binding to MMP-9 promoter. Moreover, Mw also overcame the promoting effects of PMA on B16F10 cell invasion. Mw decreased PMA-induced transcriptional activation of NF-κB and AP-1 by inhibiting phosphorylation of AKT and ERK-1/2. Furthermore, Mw strongly suppressed PMA-induced membrane localization of protein kinase C α (PKCα) since PKCα inhibition caused a marked decrease in PMA-induced MMP-9 secretion as well as AKT/ERK-1/2 activation. These results suggest that Mw may be a promising anti-invasive agent as it blocks tumor growth and inhibits B16F10 cell invasion by reducing MMP-9 activation through inhibition of PKCα/ AKT/ ERK-1/2 phosphorylation and NF-κB/AP-1 activation.
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Halder
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Shibali
authors.initials: S
authors.lastname: Das
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Bidisha Paul
authors.initials: BP
authors.lastname: Chowdhury
authors.affiliation: a Division of Molecular Medicine; Bose Institute ; Kolkata , India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009161:Mycobacterium / Q000737:chemistry*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D051571:Protein Kinase C-alpha; D020780:Matrix Metalloproteinase 9
keywords: B16F10 Melanoma; Invasion; MMP; Metastasis; Mw; PKC