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Current Medicinal Chemistry

Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Research Article

Molecular and Biochemical Evidence of Edaravone's Impact on Dasatinib-induced AGS Cell Senescence: A Promising Strategy for Gastric Cancer Therapy

Author(s): Mahban Rahimifard, Maryam Baeeri*, Mohammad Amin Manavi, Madiha Khalid, Roham Foroumadi, Hamed Haghi-Aminjan* and Mohammad Abdollahi*

Volume 33, Issue 1, 2026

Published on: 24 February, 2025

Page: [122 - 138] Pages: 17

DOI: 10.2174/0109298673338322250211111422

Price: $65

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Abstract

Introduction: Internal or external stress can induce cellular senescence, which reduces cell division. These metabolically active cells contribute to medication resistance. We examined the potential for edaravone (Eda) to cause apoptosis in dasatinib (Das)-induced senescent gastric adenocarcinoma cells (AGS). Our goal was to develop a new stomach cancer treatment.

Methods: All Eda doses evaluated were nontoxic to cells. Das decreased AGS cell survival in a dose-dependent manner. The study found that Das (5-10 μM) and Eda (100 μM) caused cell senescence in AGS cells. This was shown by increased β-galactosidase enzyme activity and reactive oxygen species levels and decreased telomerase enzyme activity. These are the biggest signs of aging.

Results: This combination therapy also upregulated the expression of cell-senescence genes p53, p16, p21, and p38. This resulted in increased expression of inflammation genes such as TNF-α, IL-1β, and IL-6.

Conclusion: The scratch assay showed that this combination medication down-regulated the cell migration-regulating matrix metalloproteinase-2 (MMP2) gene. Both Das and Eda decreased AGS cell proliferation, suggesting treatment with Eda may prevent metastasis.

Keywords: Antioxidant, chemotherapy, dasatinib, edaravone, gastric cancer, cell senescence.

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