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Involvement of AKT/PI3K Pathway in Sanguinarine's Induced Apoptosis and Cell Cycle Arrest in Triple-negative Breast

Samia S Messeha1,2, Sophie Noel1,2, Najla O Zarmouh3

  • 1Division of Pharmaceutical Sciences, College of Pharmacy & Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL, U.S.A.

Cancer Genomics & Proteomics
|July 3, 2023
PubMed
Abstract

Insights

The natural alkaloid sanguinarine (SANG) effectively reduces triple-negative breast cancer (TNBC) cell viability and induces apoptosis. SANG impacts cell cycle progression and gene expression, suggesting its potential as a novel therapeutic agent for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) exhibits significant chemotherapy resistance.
  • Developing novel therapeutic agents to overcome resistance is crucial for improving patient outcomes.
  • Natural compounds like sanguinarine (SANG) show promise as synergistic or standalone treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms of sanguinarine (SANG) in TNBC cell lines (MDA-MB-231 and MDA-MB-468).
  • To evaluate SANG's effects on cell viability, cell cycle progression, apoptosis, and gene expression.
  • To identify the signaling pathways involved in SANG-induced anticancer effects.

Main Methods:

  • Cell viability and proliferation assays (Alamar Blue).
  • Flow cytometry for cell cycle analysis and apoptosis detection.
  • Quantitative real-time PCR (qRT-PCR) apoptosis array for gene expression analysis.
  • Western blotting to assess AKT protein expression.

Main Results:

  • SANG reduced cell viability and disrupted cell cycle progression in both TNBC cell lines.
  • S-phase arrest and apoptosis were key mechanisms of growth inhibition in MDA-MB-231 cells.
  • SANG modulated the expression of apoptosis-related genes, including TNFRSF, BCL2 family, and CASP family members.
  • SANG inhibited AKT protein expression, implicating the AKT/PI3K pathway in its effects.

Conclusions:

  • SANG exhibits anticancer properties against TNBC cells by inducing cell cycle arrest and apoptosis.
  • The AKT/PI3K signaling pathway is implicated in SANG's mechanism of action.
  • SANG holds potential as a therapeutic agent, alone or in combination, for treating TNBC.
Keywords:
MDA-MB-231MDA-MB-468Sanguinarineapoptosiscell cyclegene expressionmRNAtriple-negative breast cancer

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