Document Type : Research Articles
Authors
1
Central Research Laboratory, Meenakshi Ammal Dental College, Meenakshi Academy of Higher Education and Research, deemed to be University, Chennai, India.
2
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
3
Oral Medicine and Radiology, Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, India.
4
Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, India.
Abstract
Background: Gastric cancer (GC) is a leading cause of cancer-related death worldwide, frequently associated with dysregulated PI3K/AKT/mTOR signaling and defective apoptosis. Sesamin, a lignan from sesame seeds, is rich in antioxidant and anticancer activities, yet it has not been well investigated for its therapeutic potential in GC. Objective: This study aims to investigate the anticancer potential of sesamin against gastric cancer by targeting the PI3K/AKT/mTOR signaling pathway in AGS cells and MNNG-induced rats, evaluating its effects on apoptosis, oxidative stress, and tumor biomarkers to elucidate its molecular mechanism of action. Methods: In vitro, molecular changes in AGS gastric cancer (GC) cells were determined by RT-PCR (p53, caspase-3, MDM2, PTEN, AKT, mTOR, NF-κB). In vivo, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) was used to induce gastric cancer in Wistar rats. The intervention of sesamin was studied by histopathological analysis, and ELISA was used for the measurement of tumor markers (CEA and CA 19-9) and oxidative stress markers. Gene expression was analyzed by RT-PCR (p53, caspase-3, AKT, NF-κB, mTOR). Results: Sesamin treatment in AGS cells upregulated PTEN, p53, and caspase-3, while downregulating MDM2, AKT, mTOR, and NF-κB at the mRNA level in the in vitro study. In the in vivo mRNA expression analysis, sesamin treatment confirmed enhanced p53 and caspase-3 with reduced AKT expression and slightly increased mTOR expression. In MNNG-induced rats, sesamin improved gastric histology, decreased tumor markers (CEA, CA 19-9), suppressed IL-1β, and elevated GSH. RT-PCR analysis further validated the induction of pro-apoptotic genes and suppression of oncogenic PI3K/AKT/mTOR/NF-κB signaling, consistent with in vitro findings. Conclusion: Sesamin has demonstrated effective anti-gastric cancer activity by inducing p53/caspase-3-mediated apoptosis and inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. These findings illustrate the therapeutic potential of sesamin against gastric cancer and reveal molecular clues for its use as a natural chemopreventive agent.
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