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Anti-cancer effect of midazolam via downregulating YWHAH in papillary thyroid cancer cells
Yang Li1, Ai-Ping Tan1, Yu-Shan Zhong2
1Department of Anesthesiology, The People's Hospital of SND, Suzhou, Jiangsu, 215129, People's Republic of China.
Abstract:
The work is aimed to investigate whether midazolam functions in thyroid cancer and reveal the potential mechanism of action. Cell viability was detected by CCK-8 method when treated by varying doses of midazolam to detect the cytotoxicity of midazolam on human thyroid follicular epithelial cell line and thyroid cancer cell lines. In thyroid cancer cells, EDU staining, wound healing and transwell assays were respectively used to detect cell proliferation, migration and invasion. Western blot was used to detect the expressions of matrix metalloproteinases (MMPs). Flow cytometry assay, western blot and immunofluorescence staining were used to detect cell apoptosis. CB-Dock2 server predicted midazolam-tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) interaction and western blot was also used to detect YWHAH expression. Midazolam dose-dependently decreased the viability of thyroid cancer cells and demonstrated no cytotoxicity on Nthy-ori-3-1 cells. In addition, increasing concentrations of midazolam or silencing of YWHAH significantly inhibited thyroid cancer cell proliferation, migration and invasion and induced cell apoptosis. Midazolam had a molecular binding with YWHAH and midazolam downregulated YWHAH expression. YWHAH partially reversed the impacts of midazolam on the cellular events in thyroid cancer. Collectively, midazolam may act as an anti-thyroid cancer agent via its interrelation with YWHAH.
Insights
Midazolam shows potential as an anti-thyroid cancer agent by inhibiting cancer cell viability, proliferation, migration, and invasion. It achieves this through interaction with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH).
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Thyroid cancer remains a significant health concern with ongoing research into novel therapeutic agents.
- Understanding the molecular mechanisms underlying thyroid cancer progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the anti-cancer effects of midazolam on thyroid cancer.
- To elucidate the potential mechanism of action involving tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH).
Main Methods:
- Cell viability assays (CCK-8) were used to assess midazolam's cytotoxicity.
- EDU staining, wound healing, and Transwell assays evaluated proliferation, migration, and invasion.
- Western blot, flow cytometry, and immunofluorescence detected apoptosis and protein expression (MMPs, YWHAH).
- Molecular docking (CB-Dock2) predicted midazolam-YWHAH interaction.
Main Results:
- Midazolam dose-dependently reduced thyroid cancer cell viability without affecting normal thyroid cells.
- Midazolam inhibited cancer cell proliferation, migration, and invasion while inducing apoptosis.
- Midazolam demonstrated molecular binding with YWHAH and downregulated its expression.
- YWHAH partially counteracted midazolam's effects on thyroid cancer cells.
Conclusions:
- Midazolam exhibits significant anti-thyroid cancer properties.
- The anti-cancer effects of midazolam are mediated, at least in part, through its interaction with YWHAH.
- Midazolam represents a potential therapeutic candidate for thyroid cancer treatment.
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