Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer
El-Wetidy, M., Helal, H., Rady, M. (2024). Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer. EKB Journal Management System, 16(1), 387-401. doi: 10.21608/eajbsc.2024.355267
Mohammad S. El-Wetidy; Hamed Helal; Mohamed I. Rady. "Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer". EKB Journal Management System, 16, 1, 2024, 387-401. doi: 10.21608/eajbsc.2024.355267
El-Wetidy, M., Helal, H., Rady, M. (2024). 'Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer', EKB Journal Management System, 16(1), pp. 387-401. doi: 10.21608/eajbsc.2024.355267
El-Wetidy, M., Helal, H., Rady, M. Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer. EKB Journal Management System, 2024; 16(1): 387-401. doi: 10.21608/eajbsc.2024.355267

Urolithin A Targets Both PI3K/p-AKT/mTOR and p-c-RAF/MEK/p-ERK Signaling Pathways in Colorectal Cancer

Egyptian Academic Journal of Biological Sciences. C, Physiology and Molecular Biology
Volume 16, Issue 1, June 2024, Page 387-401  XML PDF (908.02 K)
Document Type: Original Article
DOI: 10.21608/eajbsc.2024.355267
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Authors
Mohammad S. El-Wetidyorcid 1; Hamed Helalorcid 2; Mohamed I. Radyorcid 2
1Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt. -College of Medicine Research Center, King Saud University, Riyadh, 11461, Kingdom of Saudi Arabia.
2Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt.
Abstract
Urolithin A (UA) emerges as a promising natural anticancer agent and adjunct in treating colorectal cancer (CRC). This study aims to delve into the mechanism of action of UA in CRC cells. In this investigation, two colon cancer cell lines, namely HT29 and SW620, underwent treatment with specific cellular apoptotic inhibitors preceded by UA pre-treatment. The evaluation of UA's mechanism in CRC cells involved flow cytometry and western blotting. The findings revealed that apoptotic inhibitors U0126 and LY294002 mitigated the apoptotic effect of UA across all cell lines. Furthermore, in HT29, elevated levels of p-ERK and p-AMPK were observed. In SW620, the expression levels of phosphorylated AKT and the cellular proliferation regulator mTOR decreased significantly (P < 0.001), while the levels of the tumor suppressors, p-c-RAF and p-PTEN, increased. These observations suggest that UA targets the p-c-RAF/MEK/p-ERK signaling pathway in the early stages of CRC, while its mechanism in metastasis is contingent on the PI3K/p-AKT/mTOR pathway, as well. This study presents the initial evidence elucidating UA's anticancer properties by influencing these signaling pathways during both the early stages and metastasis of CRC.
Keywords
Urolithin A; Colorectal Cancer; Apoptosis; Signaling Pathway; Apoptotic inhibitors; PI3K/p-AKT/mTOR; p-c-RAF/MEK/p-ERK
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