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Melatonin Inhibits AGS Cell Proliferation by Binding to the ATP Binding Site of CDK2 Under Hyperglycemic Conditions

Abhishek Chatterjee1, Tapasi Roy1, Deeti Jyothi1

  • 1Infectious Diseases and Immunology division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700032, West Bengal, India.

Cell Biochemistry and Biophysics
|March 7, 2024
PubMed

Insights

Melatonin effectively combats gastric cancer cell proliferation exacerbated by high glucose. This study shows melatonin inhibits cancer growth by halting cell cycle progression and reducing key protein expressions.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer cells rely on glucose, with hyperglycemia worsening their aggressive proliferation.
  • Gastric cancer, specifically AGS cells, exhibits enhanced aggression under hyperglycemic conditions.

Purpose of the Study:

  • To investigate the therapeutic potential of melatonin against aggressive proliferation of human gastric cancer (AGS) cells under hyperglycemic conditions.
  • To evaluate the effects of melatonin on cell proliferation, cell cycle, apoptosis, and related molecular pathways in AGS cells.

Main Methods:

  • Cell proliferation assays, ROS generation measurement, flow-cytometry for cell cycle and apoptosis analysis.
  • Wound healing, immunoblotting, zymography, reverse zymography, in-silico analysis, and kinase activity assays were performed.
  • AGS cells were incubated in high glucose media with varying melatonin concentrations.

Main Results:

  • Melatonin significantly inhibited hyperglycemia-induced AGS cell proliferation in a dose-dependent manner.
  • Melatonin altered the expression and activity of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).
  • Melatonin induced G0/G1 cell cycle arrest by inhibiting Cyclin-dependent kinase 2 (CDK-2) kinase activity, decreasing expression of cyclin D1, cyclin E, CDK-4, and CDK-2.

Conclusions:

  • Melatonin demonstrates significant anti-gastric cancer potential by inhibiting proliferation and inducing cell cycle arrest.
  • Melatonin's mechanism involves modulating MMP-9, TIMP-1, and key cell cycle regulatory proteins.
  • Melatonin could be a valuable therapeutic agent for treating gastric cancer, especially in patients with comorbid hyperglycemia.
Keywords:
AGS cellsCDK-2Gastric CancerHyperglycemiaMMP-9Melatonin

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