Morin promotes autophagy in human PC3 prostate cancer cells by modulating AMPK/mTOR/ULK1 signaling pathway

Fereshtesadat Fakhredini1, Hadis Alidadi2, Masoud Mahdavinia3

  • 1Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Tissue & Cell
|September 12, 2024
PubMed

Insights

Morin, a natural compound, combats prostate cancer by triggering programmed cell death (apoptosis) and autophagy. It activates AMP-activated protein kinase (AMPK) and ULK1 while inhibiting mTOR, leading to cancer cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • AMP-activated protein kinase (AMPK) plays a crucial role in suppressing tumor growth by regulating autophagy and apoptosis.
  • Understanding the molecular mechanisms underlying cancer progression is vital for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the impact of Morin on PC3 prostate cancer cells.
  • To elucidate the role of the AMPK/mTOR/ULK1 pathway and autophagy in Morin-induced anti-cancer effects.

Main Methods:

  • PC3 cells were treated with Morin and AICAR (an AMPK activator).
  • Assessed cell viability, apoptosis (DAPI staining, Bax/Bcl-2 ratio, Caspase activity, Annexin V/PI), and autophagy markers (LC3B/LC3A ratio, Acridine Orange staining, Beclin-1, ATG5, p62).
  • Analyzed protein levels of p-AMPK, p-ULK1, and p-mTOR.

Main Results:

  • Morin significantly reduced PC3 cell viability and induced apoptosis.
  • Morin treatment increased p-AMPK and p-ULK1 levels while decreasing p-mTOR expression.
  • Morin promoted autophagy, evidenced by increased LC3B/LC3A ratio and Beclin-1/ATG5 expression, and decreased p62 levels.
  • AICAR enhanced Morin's anti-cancer effects, further supporting the role of AMPK activation.

Conclusions:

  • Morin induces apoptotic and autophagic cell death in PC3 prostate cancer cells.
  • The mechanism involves the activation of the AMPK/ULK1 pathway and suppression of the mTOR pathway.
  • Morin shows potential as a therapeutic agent for prostate cancer.

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