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Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast

Reihaneh Fatehi1, Mohammad Nouraei2,1, Morteza Panahiyan2,1

  • 1Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Biochemistry and Biophysics Reports
|June 4, 2024
PubMed

Insights

Sertraline and related renin-angiotensin system (RAS) drugs show anti-cancer effects against breast cancer cells. These compounds reduce cell viability and promote apoptosis, offering potential new strategies for breast cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • The renin-angiotensin system (RAS) is crucial for cardiovascular function but is implicated in cancer progression and metastasis.
  • Breast cancer, a leading cause of cancer mortality in women, presents ongoing prevention challenges.
  • RAS components are present in breast tissue, suggesting a role in cancer pathology.

Purpose of the Study:

  • To investigate the anti-cancer effects of sertraline, an antidepressant with known anti-proliferative properties.
  • To evaluate the impact of combining sertraline with RAS modulators (A779, Ang 1-7, losartan) on breast cancer cells.
  • To assess the effects on cell viability, apoptosis, and cell cycle distribution in MCF-7 cells.

Main Methods:

  • Treatment of MCF-7 breast cancer cells with sertraline, losartan, Ang 1-7, and A779, individually and in combination.
  • Assessment of cell viability, apoptosis induction, and cell cycle distribution.
  • Evaluation of reactive oxygen species (ROS) generation.

Main Results:

  • Sertraline, losartan, and Ang 1-7 significantly reduced MCF-7 cell viability and induced apoptosis and cell cycle arrest.
  • The RAS antagonist A779 diminished the effects of sertraline on cell viability, ROS generation, and cell cycle arrest.
  • Combination therapy with sertraline and losartan or Ang 1-7 resulted in a substantial decrease in cell viability.

Conclusions:

  • Sertraline exhibits anti-cancer properties against breast cancer cells.
  • Losartan and Ang 1-7 also demonstrate anti-cancer effects, acting via apoptosis and cell cycle arrest.
  • Targeting the RAS pathway in conjunction with sertraline may offer a promising therapeutic strategy for breast cancer.
Keywords:
AT1 receptorAngiotensin 1-7Breast cancerLosartanMas receptorRenin-angiotensin systemSertraline

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