Mycobacterium indicus pranii (Mw) inhibits invasion by reducing matrix metalloproteinase (MMP-9) via AKT/ERK-1/2 and PKCa signalling: a potential candidate in melanoma cancer therapy.
Kuntal Halder
Sayantan Banerjee
Sweta Ghosh
Anamika Bose
Shibali Das
Bidisha Paul Chowdhury
Subrata Majumdar
Cancer biology & therapy
PubMedID: 26390181
Halder K, Banerjee S, Ghosh S, Bose A, Das S, Chowdhury BP, Majumdar S. Mycobacterium indicus pranii (Mw) inhibits invasion by reducing matrix metalloproteinase (MMP-9) via AKT/ERK-1/2 and PKCa signalling: a potential candidate in melanoma cancer therapy. Cancer Biol Ther. 2015;0.
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-?B (NF-?B) 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-?B and AP-1 by inhibiting phosphorylation of AKT and ERK-1/2. Furthermore, Mw strongly suppressed PMA-induced membrane localization of protein kinase C a (PKCa) since PKCa 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 PKCa/ AKT/ ERK-1/2 phosphorylation and NF-?B/AP-1 activation.
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