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Small-Molecule Endoplasmic Reticulum Stress Inducer Triggers Apoptosis in Cancer Cells

Jaypalsing Ingle1, Anjana Tirkey1, Shalini Pandey1

  • 1Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, 382355, Gandhinagar, Gujarat, India.

Chemmedchem
|November 15, 2023
PubMed

Insights

Researchers developed a novel small molecule that targets the endoplasmic reticulum (ER), inducing ER stress and apoptosis in cancer cells. This discovery offers a new avenue for developing ER-targeted cancer therapeutics.

Area of Science:

  • Cell Biology
  • Medicinal Chemistry
  • Oncology

Background:

  • The endoplasmic reticulum (ER) is crucial for protein synthesis, modification, and signaling, maintaining cellular homeostasis.
  • ER dysfunction causes ER stress, implicated in various diseases, including cancer.
  • Targeting ER stress is a potential cancer therapeutic strategy, but ER-specific small molecules are lacking.

Purpose of the Study:

  • To synthesize and screen a library of novel small molecules for ER targeting.
  • To identify a small molecule that induces ER stress and apoptosis in cancer cells.
  • To explore the potential of this molecule as an ER-targeted cancer therapeutic.

Main Methods:

  • Synthesis of a 3-methoxy-pyrrole-enamine library.
  • Screening of the library in cervical, colon, breast, and lung cancer cell lines.
  • Confocal microscopy for ER localization, Western blotting for ER stress markers, and apoptosis assays.

Main Results:

  • A novel small molecule was identified that localizes to the ER in HeLa cervical cancer cells within 3 hours.
  • This molecule significantly increased ER stress markers (CHOP, IRE1α, PERK, BiP, Cas-12).
  • The molecule triggered apoptosis and led to substantial HeLa cell death.

Conclusions:

  • A novel ER-targeting small molecule was successfully synthesized and validated.
  • This molecule effectively induces ER stress and apoptosis in cancer cells.
  • The findings support further investigation of this molecule for developing novel ER-targeted cancer therapeutics.
Keywords:
3-methoxypyrrole-enamineER stressapoptosiscancerendoplasmic reticulum

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