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Atiprimod triggered apoptotic cell death via acting on PERK/eIF2α/ATF4/CHOP and STAT3/NF-ΚB axis in MDA-MB-231 and

Ajda Coker-Gurkan1, Esin Can2, Semanur Sahin2

  • 1Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Topkapı Campus, 34010, Istanbul, Turkey. ajdaaacoker@gmail.com.

Molecular Biology Reports
|July 10, 2021
PubMed
Abstract

Insights

Atiprimod triggers breast cancer cell death by inducing endoplasmic reticulum stress and inhibiting STAT3/NF-κB pathways. This study reveals its potential as a novel therapeutic agent for triple-negative breast cancer (TBNC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Constitutive activation of STAT3 drives breast cancer growth and metastasis.
  • Atiprimod exhibits anti-cancer effects in various cancers by inhibiting STAT3.
  • The role of atiprimod in breast cancer, particularly its mechanism involving ER stress, remains unexplored.

Purpose of the Study:

  • To investigate the therapeutic efficiency and mechanistic action of atiprimod in MDA-MB-231 and MDA-MB-468 breast cancer cells.
  • To elucidate the role of endoplasmic reticulum (ER) stress in atiprimod-induced apoptosis.

Main Methods:

  • Dose- and time-dependent treatment of breast cancer cells (MDA-MB-468, MDA-MB-231) with atiprimod.
  • Assessment of cell viability, colony formation, and protein expression levels (STAT3, p65, PERK, BiP, ATF-4, CHOP, etc.).
  • Analysis of protein phosphorylation and nuclear localization of transcription factors (STAT1, STAT3, NF-κB).

Main Results:

  • Atiprimod significantly inhibited cell viability and colony formation in both cell lines.
  • Atiprimod suppressed STAT3 phosphorylation and p65 expression, preventing nuclear translocation of STAT1, STAT3, and NF-κB.
  • Atiprimod induced ER stress by upregulating PERK, BiP, ATF-4, CHOP, and activating the PERK/eIF2α/ATF4/CHOP axis, leading to G1/S arrest and apoptosis.

Conclusions:

  • Atiprimod induces apoptosis in triple-negative breast cancer (TBNC) cells through prolonged ER stress.
  • The mechanism involves activation of the PERK/eIF2α/ATF4/CHOP pathway and suppression of STAT3/NF-κB nuclear migration.
  • Atiprimod demonstrates potential as a therapeutic agent for TBNC by modulating ER stress and key signaling pathways.
Keywords:
ApoptosisAtiprimodAutophagyCancerCell cycleEndoplasmic reticulum

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