open access

Vol 54, No 4 (2016)
Original paper
Submitted: 2016-03-21
Accepted: 2016-11-21
Published online: 2016-11-29
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Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

Deniz Ogut, Buket Reel, Ceren Gonen Korkmaz, Mehmet Zuhuri Arun, Serap Cilaker Micili, Bekir Ugur Ergur
DOI: 10.5603/FHC.a2016.0022
·
Pubmed: 27966209
·
Folia Histochem Cytobiol 2016;54(4):171-180.

open access

Vol 54, No 4 (2016)
ORIGINAL PAPERS
Submitted: 2016-03-21
Accepted: 2016-11-21
Published online: 2016-11-29

Abstract

Introduction. Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-κB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-κB signaling.

Material and methods. PC3 cells were incubated with LPS (0.5 μg/mL) for 24 h in the presence or absence of doxycycline (5 μg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-κB/p65, IκB-α, p-IκB-α, IKK-β were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography.

Results. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-κB /p65, p-IκB-α, IKK-β and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IκB-α was affected by neither LPS nor doxycycline.

Conclusions. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-κB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.

Abstract

Introduction. Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-κB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-κB signaling.

Material and methods. PC3 cells were incubated with LPS (0.5 μg/mL) for 24 h in the presence or absence of doxycycline (5 μg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-κB/p65, IκB-α, p-IκB-α, IKK-β were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography.

Results. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-κB /p65, p-IκB-α, IKK-β and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IκB-α was affected by neither LPS nor doxycycline.

Conclusions. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-κB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.

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Keywords

prostate cancer; PC3 cells; MMPs; doxycycline; NF-kB; immunohistochemistry; Western blotting; zymography

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About this article
Title

Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 54, No 4 (2016)

Article type

Original paper

Pages

171-180

Published online

2016-11-29

DOI

10.5603/FHC.a2016.0022

Pubmed

27966209

Bibliographic record

Folia Histochem Cytobiol 2016;54(4):171-180.

Keywords

prostate cancer
PC3 cells
MMPs
doxycycline
NF-kB
immunohistochemistry
Western blotting
zymography

Authors

Deniz Ogut
Buket Reel
Ceren Gonen Korkmaz
Mehmet Zuhuri Arun
Serap Cilaker Micili
Bekir Ugur Ergur

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