Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells
Deniz Ogut, Buket Reel1, Ceren Gonen Korkmaz
1Department of Pharmacology, Faculty of Pharmacy, Ege University, Bornova-Izmir. buket.reel@ege.edu.tr.
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.
Insights
Doxycycline inhibits matrix metalloproteinase (MMP) expression and activity in prostate cancer cells. This study shows doxycycline's potential in targeting MMPs and NF-κB signaling in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Matrix metalloproteinase (MMP) enzymes degrade extracellular matrix, promoting inflammation, cancer cell proliferation, invasion, and angiogenesis.
- Doxycycline, a tetracycline derivative, inhibits MMPs at subantimicrobial doses, impacting tumor growth and spread.
- Aberrant nuclear factor kappa B (NF-κB) signaling activates MMPs, driving cancer cell proliferation and invasion.
Purpose of the Study:
- To investigate doxycycline's effects on MMP expression in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells.
- To explore the potential role of NF-κB signaling in regulating MMPs in this model.
Main Methods:
- PC3 cells were treated with LPS and doxycycline.
- Expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-κB/p65, IκB-α, p-IκB-α, and IKK-β were analyzed via Western blotting and immunohistochemistry.
- MMP-2 and MMP-9 activities were assessed using gelatin zymography.
Main Results:
- LPS upregulated MMP-9 activity and expression of MMP-8, MMP-10, NF-κB/p65, p-IκB-α, and IKK-β.
- Doxycycline counteracted most LPS-induced effects, except for MMP-10 expression.
- MMP-2 and IκB-α expression remained unaffected by LPS or doxycycline.
Conclusions:
- Doxycycline effectively inhibits the expression of several MMPs in LPS-induced prostate cancer cells.
- NF-κB signaling appears to play a role in regulating MMP expression within this cancer model.
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