Title:Molecular and Biochemical Evidence of Edaravone's Impact on
Dasatinib-induced AGS Cell Senescence: A Promising Strategy for
Gastric Cancer Therapy
Volume: 33
Issue: 1
Author(s): Mahban Rahimifard, Maryam Baeeri*, Mohammad Amin Manavi, Madiha Khalid, Roham Foroumadi, Hamed Haghi-Aminjan*Mohammad Abdollahi*
Affiliation:
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Antioxidant, chemotherapy, dasatinib, edaravone, gastric cancer, cell senescence.
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.
