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Anti-Cancer Role of Ellagic Acid by Modulating the Altered PI3K/PTEN/Akt Pathway in Bladder Cancer
Satya Sahay1, Deepika Trehan2, Ranbala Kumari3
1Lab-CRIB, ICMR-National Institute of Pathology, Delhi 110029, India.
Abstract:
Bladder cancer (BCa) is approximately the fourth most prevalent diagnosed cancer in men and is three times less common in women. Therefore, identifying biomarkers, developing more effective therapeutic strategies, and understanding the mechanisms underlying BCa tumor growth and progression are urgently required to improve survival rates. Therefore, we aim to investigate the expression of PTEN/Akt in tissue samples of both non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients (n = 70) and human BCa cell lines T24 and 5637, along with the potent role of ellagic acid (EA) in the modulation of the PTEN/Akt pathway and the resulting therapeutic potential. Results showed low-intensity nuclear or cytoplasmic PTEN staining or loss of PTEN expression in tumor cells and overexpression of p-Akt (Ser-473) with high intensity in the nucleus or cytoplasm. EA treatment of T24 and 5637 cells reduced cell viability, inflammation (NF-κB, COX-2), invasion (MMP-9), induced the caspase (cas-3 and cas-9) cascade signaling pathway, and induced cell apoptosis along with the suppression of the PI3K/PTEN/Akt signaling pathway after 48h in a dose-dependent manner. Thus, these data suggested that the EA showed a strong potential anti-cancer effect in T24 and 5637 cells. In conclusion, the expression of PTEN/p-Akt and the inverse relation indicated an alteration of the PTEN/Akt pathway, and such cases could benefit from treatment with EA in BCa.
Insights
Ellagic acid (EA) shows potential in treating bladder cancer (BCa). It targets the PTEN/Akt pathway, reducing cancer cell viability and promoting apoptosis in BCa models.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer (BCa) is a significant health concern, particularly in men.
- Improved therapeutic strategies and understanding of BCa progression are crucial for better survival rates.
- The PTEN/Akt pathway plays a critical role in cancer development and progression.
Purpose of the Study:
- To investigate PTEN/Akt expression in non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC).
- To evaluate the therapeutic potential of ellagic acid (EA) in modulating the PTEN/Akt pathway in BCa.
- To analyze the effects of EA on BCa cell lines T24 and 5637.
Main Methods:
- Analysis of PTEN and p-Akt expression in 70 BCa patient tissue samples.
- Treatment of human BCa cell lines (T24, 5637) with varying doses of EA.
- Assessment of cell viability, inflammation markers (NF-κB, COX-2), invasion (MMP-9), apoptosis (caspase cascade), and PTEN/Akt pathway activity.
Main Results:
- Tumor cells exhibited low PTEN expression or loss, with concurrent overexpression of p-Akt.
- EA treatment significantly reduced BCa cell viability, inflammation, and invasion.
- EA induced apoptosis and suppressed the PI3K/PTEN/Akt pathway in a dose-dependent manner.
Conclusions:
- Altered PTEN/Akt pathway expression (low PTEN, high p-Akt) is associated with BCa.
- Ellagic acid demonstrates significant anti-cancer effects against BCa cell lines.
- Patients with altered PTEN/Akt pathway may benefit from EA-based therapies for bladder cancer.
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