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Updated: Jun 28, 2025

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

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Novel combinatorial autophagy inhibition therapy for triple negative breast cancers

Yomna S Abd El-Aziz1, Taymin du Toit-Thompson2, Matthew J McKay3

  • 1Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, Australia; Oral Pathology Department, Faculty of Dentistry, Tanta University, Tanta, Egypt.

European Journal of Pharmacology
|April 11, 2024
PubMed
Abstract

Insights

Targeting autophagy with novel drug combinations shows promise for treating triple negative breast cancer (TNBC). This approach inhibits tumor cell proliferation in both sensitive and resistant TNBC models, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Triple negative breast cancer (TNBC) presents a poor prognosis due to limited treatment options.
  • Autophagy is linked to aggressive TNBC behavior and poor patient outcomes.
  • This study investigates targeting autophagy as a novel strategy to combat TNBC progression.

Purpose of the Study:

  • To explore the role of autophagy in TNBC progression.
  • To evaluate novel autophagy inhibitors for TNBC treatment.
  • To identify synergistic combinations of autophagy inhibitors.

Main Methods:

  • Examined autophagy induction by microenvironmental stressors using immunoblotting and microscopy.
  • Assessed proliferation and migration effects of autophagy inhibitors and chemotherapy.
  • Utilized in vivo xenograft models and proteomic analysis to study chemoresistance mechanisms.

Main Results:

  • Metabolic stressors induce autophagy in TNBC cell lines.
  • Autophagy inhibitors SAR405 and MRT68921 demonstrated synergistic anti-proliferative effects.
  • Contrary to expectations, LC3 expression correlated with better TNBC patient survival.

Conclusions:

  • A novel combination of autophagy inhibitors effectively inhibits TNBC cell proliferation.
  • This combination shows potential as a new treatment modality for TNBC.
  • Further research into autophagy modulation could lead to improved TNBC therapies.
Keywords:
AutophagyAutophagy inhibitorsChemoresistanceTriple negative breast cancer

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