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Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells

Shalini Pandey1,2, Virender Kumar Sharma3, Ankur Biswas1

  • 1Department of Chemistry, Indian Institute of Science Education and Research (IISER)-Pune Homi Bhabha Road, Pashan Pune 411008 India ankur.biswas@students.iiserpune.ac.in.

RSC Medicinal Chemistry
|October 21, 2021
PubMed

Insights

Researchers developed a novel small molecule targeting the endoplasmic reticulum (ER) to induce cancer cell death. This molecule triggers ER stress and apoptosis, showing promise for new anticancer therapies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Drug Discovery

Background:

  • The endoplasmic reticulum (ER) is vital for protein homeostasis and its dysfunction is linked to cancer.
  • Targeting the ER presents a novel strategy for cancer therapy, but selective small molecules are lacking.

Purpose of the Study:

  • To develop and evaluate novel small molecules for selective ER targeting in cancer therapy.
  • To investigate the mechanism of action of a novel ER-targeting small molecule.

Main Methods:

  • Synthesis of a sulfonylhydrazide-hydrazone small molecule library.
  • Fluorescent imaging to confirm ER localization in HeLa cells.
  • Assessment of ER stress, autophagy induction, and apoptosis in cancer cells.

Main Results:

  • A novel fluorescent small molecule was identified that localizes to the ER.
  • The molecule induced ER stress and triggered autophagy, which, when inhibited by chloroquine, led to apoptosis.
  • Significant cancer cell killing efficacy was observed in mono and combination therapy.

Conclusions:

  • The developed small molecule effectively targets the ER and induces cancer cell death.
  • This study opens a new avenue for ER-targeted anticancer drug development.

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