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The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum

Yanshan Zheng1, Jiawei Tu1, Xinxin Wang1

  • 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People's Republic of China.

Oncotargets and Therapy
|February 18, 2020
PubMed
Abstract

Insights

Melatonin inhibits gastric cancer (GC) growth by inducing endoplasmic reticulum (ER) stress, leading to apoptosis and autophagy. This process is mediated by the IRE1/JNK/Beclin1 signaling pathway, offering a potential therapeutic strategy for GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Gastric cancer (GC) presents a significant global health challenge with high mortality rates due to limited effective treatments.
  • Melatonin, a natural compound, exhibits anti-cancer properties, but its precise mechanisms in GC remain unclear.
  • Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in tumor progression and chemoresistance, often involving autophagy.

Purpose of the Study:

  • To investigate the effects of melatonin on human gastric cancer cell lines (AGS and SGC-7901).
  • To elucidate the interaction between melatonin, ER stress, and autophagy in the context of gastric cancer.
  • To identify the specific signaling pathways involved in melatonin's anti-gastric cancer effects.

Main Methods:

  • Cell viability (CCK-8), migration (wound healing), and colony formation assays were performed.
  • Immunofluorescence, Western blotting, and flow cytometry were utilized to assess cellular processes.
  • In vivo animal models were employed to evaluate melatonin's efficacy and mechanisms.

Main Results:

  • Melatonin demonstrated significant inhibition of gastric cancer growth, proliferation, and invasion both in vitro and in vivo.
  • Melatonin induced apoptosis and autophagy in a concentration-dependent manner, linked to ER stress.
  • Inhibition of ER stress (4-PBA) and autophagy (3-MA) attenuated melatonin's effects; IRE1 inhibition reduced autophagy markers (LC3-II, Beclin-1).

Conclusions:

  • Melatonin effectively inhibits gastric cancer cell proliferation through the induction of ER stress.
  • The study identified the IRE1/JNK/Beclin1 signaling pathway as crucial for melatonin's anti-gastric cancer activity.
  • Melatonin represents a promising therapeutic agent for gastric cancer, with its action mediated by ER stress and autophagy.
Keywords:
Jun N-terminal kinaseapoptosisautophagyendoplasmic reticulum stressinositol-requiring 1αmelatonin

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