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Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis

Myoung Suk Choi1, Dong Yeon Yuk, Ju Hoon Oh

  • 1College of Pharmacy Medical Science and Engineering Research Center, Chungbuk National University 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.

Anticancer Research
|February 5, 2009
PubMed

Insights

Berberine shows anticancer effects against neuroblastoma cells by inducing p53-dependent apoptosis. This natural compound may serve as a potential therapeutic agent for neuroblastoma treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Berberine, a natural alkaloid, exhibits anti-tumor properties in various cancer cells.
  • The precise mechanisms underlying berberine's anticancer activity remain incompletely understood.

Purpose of the Study:

  • To investigate the anticancer effects of berberine on human neuroblastoma cell lines (SK-N-SH and SK-N-MC).
  • To elucidate the molecular mechanisms involved in berberine-induced cell death, particularly focusing on the role of p53.

Main Methods:

  • Cell viability assays (IC50 determination) were performed on neuroblastoma and cortical neuronal cells.
  • Cell cycle progression and apoptosis were analyzed using flow cytometry.
  • Expression levels of cell cycle regulators (cyclins, CDKs) and apoptosis-related genes were assessed.
  • The role of p53 was investigated using p53 siRNA and a p53 inhibitor (pifithrin-alpha).

Main Results:

  • Berberine demonstrated higher susceptibility in p53-expressing SK-N-SH cells (IC50=37 microM) compared to p53-deficient SK-N-MC cells (IC50 > or =100 microM).
  • Berberine induced G0/G1 cell cycle arrest and apoptotic cell death, with more pronounced effects in SK-N-SH cells.
  • Berberine decreased the expression of cyclin D1, cyclin E, Cdk2, and Cdk4, while increasing apoptotic gene expression and caspase-3 activation in SK-N-SH cells.
  • Inhibition of p53 function led to increased cell viability and reduced berberine-induced apoptosis and caspase-3 activation.

Conclusions:

  • Berberine induces p53-dependent apoptotic death in human neuroblastoma cells.
  • The findings suggest that berberine's anticancer mechanism involves the regulation of cell cycle progression and apoptosis via a p53-mediated pathway.
  • Berberine holds potential as a therapeutic agent for neuroblastoma.

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