Cell cycle arrest-mediated cell death by morin in MDA-MB-231 triple-negative breast cancer cells

Sushma Maharjan1, Yun-Suk Kwon1, Min-Gu Lee1

  • 1Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, 38066, Republic of Korea.

Abstract

Insights

Morin, a flavonoid, effectively inhibits triple-negative breast cancer cell proliferation by inducing sustained cell cycle arrest. This occurs through ERK activation and FOXM1 repression, leading to cell death without apoptosis.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • Morin, a flavonoid from the Moraceace family, possesses known pharmacological activities, including anti-cancer properties.
  • While morin's anti-cancer effects on breast cancer have been studied, its precise pharmaceutical mechanisms remain incompletely understood.
  • This study focuses on elucidating the detailed signaling pathways involved in morin's action on MDA-MB-231 triple-negative breast cancer cells.

Purpose of the Study:

  • To investigate the detailed signaling pathway of morin in MDA-MB-231 triple-negative breast cancer cells.
  • To understand the mechanism of morin-induced anti-cancer effects.
  • To explore morin's impact on cell proliferation, cell cycle, and cell death.

Main Methods:

  • Cytotoxicity was assessed using sulforhodamine B (SRB) and colony formation assays.
  • Flow cytometry was employed to analyze cell cycle progression and cell death patterns.
  • Western blotting was used to detect protein expression and phosphorylation levels.

Main Results:

  • Morin demonstrated dose- and time-dependent inhibition of MDA-MB-231 cell proliferation, inducing morphological changes.
  • Morin triggered ERK and p-H2A.X phosphorylation while decreasing RAD51 and survivin levels.
  • Cell cycle analysis revealed S and G2/M phase arrest, linked to reduced cyclin A2/B1 and increased p21 expression. Morin induced non-apoptotic cell death and attenuated FoxM1, correlating with cell cycle regulators.

Conclusions:

  • Morin induces cell death in MDA-MB-231 cells through sustained cell cycle arrest.
  • This arrest is mediated by p21 induction via ERK activation.
  • The mechanism also involves the repression of FOXM1 signaling pathways.

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