Journal
CANCER BIOLOGY & THERAPY
Volume 18, Issue 11, Pages 850-862Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2015.1078024
Keywords
B16F10 Melanoma; Invasion; Metastasis; Mw; MMP; PKC
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Funding
- Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi
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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-kappa B (NF-kappa 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-kappa 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 alpha (PKC alpha) since PKC alpha 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 PKC alpha/AKT/ERK-1/2 phosphorylation and NF-kappa B/AP-1 activation.
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