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S4 Induces Apoptosis, Cell Cycle Arrest, and Metabolic Alterations in Breast Cancer Cells

Mervenur Yavuz1, Turan Demircan2

  • 1Department of Molecular Biology and Genetics, Institute of Natural Sciences, Muğla Sıtkı Koçman University, Muğla, Turkey.

Anti-Cancer Agents in Medicinal Chemistry
|August 24, 2026
PubMed
Abstract

Insights

Selective androgen receptor modulators (SARMs), like S4 (Andarine), show significant anti-cancer effects in breast cancer models by altering cell viability and metabolism. Further research into SARMs for breast cancer treatment is warranted.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolomics

Background:

  • Breast cancer (BC) is a leading cause of cancer mortality worldwide.
  • Androgen receptor (AR) signaling influences breast oncology.
  • The therapeutic potential of selective androgen receptor modulators (SARMs), specifically S4 (Andarine), in BC is not well understood.

Purpose of the Study:

  • To investigate the anti-cancer activity and underlying mechanisms of S4 in different breast cancer subtypes.
  • To evaluate the impact of S4 on cellular functions and metabolic pathways.

Main Methods:

  • S4 efficacy was tested on Estrogen Receptor-positive (MCF-7) and Triple-Negative (MDA-MB-231) breast cancer cell lines.
  • Assays included cellular viability, clonogenicity, migration, apoptosis, and cell cycle analysis.
  • Mechanisms were explored using gene expression profiling and LC-MS-based metabolomics.

Main Results:

  • S4 significantly reduced viability, clonogenicity, and migration in a dose-dependent manner.
  • S4 induced apoptosis and cell cycle arrest (S-phase in MCF-7, G0/G1-S in MDA-MB-231).
  • Metabolomic and gene expression analyses revealed significant remodeling of metabolic pathways and modulation of key regulatory genes.

Conclusions:

  • S4 treatment alters breast cancer cell growth and key metabolic pathways.
  • The metabolic response to S4 is coordinated but context-dependent, with subtype-specific adaptations.
  • S4 may exploit unique metabolic vulnerabilities, supporting its further investigation in breast cancer treatment strategies.
Keywords:
Breast cancerandarineapoptosiscell-cycle arrestmetabolomicsselective androgen receptor modulator

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