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Published on: August 2, 2024
Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway
Sahar Baghal-Sadriforoush1, Morteza Bagheri2, Isa Abdi Rad3
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. sbaghalsadriforoush@yahoo.com.
Abstract:
This study examined the effect of melatonin on oxidative stress, expression of pro-apoptotic protein, anti-apoptotic proteins, and the activity of the PI3K/Akt signaling pathway in the human ovarian cancer cell line (OVCAR3). OVCAR3 cells were treated with cisplatin, melatonin, cisplatin + melatonin, and siRNA Akt. Reactive oxygen species levels were assessed. The expression of the proteins was determined by Western blot. Melatonin administration significantly increased intracellular ROS generation, the cleavage of caspase 3 and decreased phosphorylation of Akt. Combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibiting of PI3K/Akt signaling pathway and exacerbating oxidative stress.
Insights
Melatonin enhances cisplatin
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ovarian cancer remains a significant health challenge.
- Understanding molecular pathways like PI3K/Akt is crucial for treatment.
- Melatonin's role in cancer therapy is an area of active research.
Purpose of the Study:
- To investigate melatonin's effects on oxidative stress and apoptosis in ovarian cancer cells.
- To determine melatonin's impact on the PI3K/Akt signaling pathway.
- To evaluate combination therapy with cisplatin and melatonin.
Main Methods:
- Ovarian cancer cells (OVCAR3) were treated with cisplatin, melatonin, or both.
- Reactive oxygen species (ROS) levels were measured.
- Protein expression and signaling pathway activity (PI3K/Akt) were analyzed via Western blot.
Main Results:
- Melatonin increased reactive oxygen species (ROS) and caspase 3 cleavage, indicating enhanced apoptosis.
- Melatonin decreased Akt phosphorylation, suggesting PI3K/Akt pathway inhibition.
- Combined cisplatin and melatonin therapy amplified apoptosis and oxidative stress.
Conclusions:
- Melatonin potentiates cisplatin's anti-cancer effects in OVCAR3 cells.
- The combination therapy inhibits the PI3K/Akt pathway and increases oxidative stress.
- Melatonin shows promise as an adjuvant therapy for ovarian cancer.
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