Clinoptilolite inhibits αvβ1 integrin-mediated matrix metalloproteinase up-regulation in PC3 cells
DOI:
https://doi.org/10.1590/s2175-97902026e24892Palavras-chave:
Prostate cancer. PC3. Clinoptilolite. Integrin. Matrix metalloproteinase.Resumo
Prostate cancer changes from an androgen-dependent to an independent type during its progression, and metastasis greatly limits treatment options and survival rates. Matrix metalloproteinases (MMPs) play an essential role in inflammation, malignant cell proliferation, invasion, and metastasis by inducing matrix degradation. Endogenous tissue inhibitors of MMPs (TIMPs) limit the activities of MMPs. The integrin signalling regulates cancer cell adhesion, proliferation, and migration by promoting MMP activation. Clinoptilolite is a micronized type of zeolite, which is a hydrated aluminosilicate. It is used as a chelation and detoxification agent to remove heavy metals from the body. This study investigated the effects of clinoptilolite on the expression and/or activity of gelatinases (MMP-2/MMP-9), MMP-14, TIMP-2, and αvβ1 integrin in PC3 cells. PC3 cells were incubated with/without clinoptilolite (25 mg/ml) for 24 h. The expression and/or activity of MMP-2 and MMP-9 were determined by gelatin zymography. The expression levels of MMP-14, TIMP-2, and αvβ1 were examined by immunostaining. Clinoptilolite inhibited MMP-2 activity and MMP-14 expression while up-regulating TIMP-2 expression, and it decreased MMP-2/TIMP-2 and MMP-14/TIMP-2 ratios, which are critical for MMP/TIMP balance. Clinoptilolite also down-regulated αvβ1 integrin expression. Clinoptilolite may be useful in prostate cancer treatment due to its αvβ1 integrin-mediated MMP inhibitory effects.
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