Sesamin Mitigates Gastric Carcinogenesis via Modulation of the PI3K/AKT/mTOR Signaling Pathway in AGS Cells and

Manju Parthiban1, Ponnulakshmi Rajagopal1, Heera Maheswari Jayaveeran1

  • 1Central Research Laboratory, Meenakshi Ammal Dental College, Meenakshi Academy of Higher Education and Research, deemed to be University, Chennai, India.

Abstract

Insights

Sesamin shows promise as a natural gastric cancer treatment by inducing apoptosis and inhibiting the PI3K/AKT/mTOR/NF-κB pathway. This study highlights sesamin

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Product Chemistry

Background:

  • Gastric cancer (GC) is a major global health concern, often linked to aberrant PI3K/AKT/mTOR signaling and impaired apoptosis.
  • Sesamin, a sesame lignan, possesses known antioxidant and anticancer properties but its therapeutic role in GC remains underexplored.

Purpose of the Study:

  • To investigate sesamin's anticancer effects on gastric cancer (AGS cells and MNNG-induced rats).
  • To evaluate sesamin's impact on apoptosis, oxidative stress, and tumor biomarkers.
  • To elucidate the molecular mechanism involving the PI3K/AKT/mTOR pathway.

Main Methods:

  • In vitro: RT-PCR analysis of key genes (p53, caspase-3, MDM2, PTEN, AKT, mTOR, NF-κB) in AGS cells.
  • In vivo: MNNG-induced gastric cancer in Wistar rats, followed by histopathology, ELISA for tumor/oxidative stress markers, and RT-PCR for gene expression.

Main Results:

  • Sesamin upregulated pro-apoptotic genes (PTEN, p53, caspase-3) and downregulated pro-survival genes (MDM2, AKT, mTOR, NF-κB) in AGS cells.
  • In vivo, sesamin improved gastric histology, reduced tumor markers (CEA, CA 19-9), and modulated oxidative stress markers (elevated GSH, suppressed IL-1β).
  • Gene expression analysis confirmed sesamin's induction of apoptosis and inhibition of the PI3K/AKT/mTOR/NF-κB pathway.

Conclusions:

  • Sesamin exhibits significant anti-gastric cancer activity through p53/caspase-3-mediated apoptosis induction.
  • Sesamin effectively inhibits the PI3K/AKT/mTOR/NF-κB signaling pathway in gastric cancer models.
  • Sesamin demonstrates potential as a natural chemopreventive agent for gastric cancer.

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