التفاصيل البيبلوغرافية
| العنوان: |
Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity. |
| المؤلفون: |
Jung, Jinkyu, Celiku, Orieta, Rubin, Benjamin I., Gilbert, Mark R. |
| المصدر: |
Cancers; Jun2024, Vol. 16 Issue 11, p2029, 12p |
| مصطلحات موضوعية: |
IN vitro studies, CELL migration inhibition, CELL migration, GLIOMAS, CANCER invasiveness, RESEARCH funding, BLOOD-brain barrier, ENZYME-linked immunosorbent assay, TUMOR markers, SMALL molecules, CELL lines, MATRIX metalloproteinases, MICROBIOLOGICAL assay, WESTERN immunoblotting |
| مستخلص: |
Simple Summary: Cysteamine, an endogenously synthesized agent in mammalian cells and FDA-approved for cystinosis, shows promise as a safe anti-cancer agent by inhibiting tumor cell invasion and metastasis. Using computational analyses and multiple glioblastoma cell lines, we demonstrate the in vitro drug efficacy and molecular mechanism by which cysteamine inhibits tumor invasion and migration through targeting matrix metalloproteinase activity at micromolar concentrations. Our findings suggest that cysteamine could represent a novel therapeutic option for the treatment of glioblastoma patients. Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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