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Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells

Ana Belén Granado-Serrano1, María Angeles Martín, Laura Bravo

  • 1Instituto del Frío-Instituto de Ciencia y Tecnología de Alimentos y Nutrición, Madrid, Spain.

Nutrition and Cancer
|April 2, 2010
PubMed

Insights

Quercetin, a flavonoid, inhibits cancer cell growth by altering key signaling pathways. It inactivates NF-kappa B and activates AP-1/JNK, leading to programmed cell death in liver cancer cells.

Area of Science:

  • * Molecular Biology
  • * Cellular Biology
  • * Biochemistry

Background:

  • * Quercetin is a dietary flavonoid with demonstrated anticarcinogenic potential.
  • * The molecular mechanisms underlying quercetin's anti-cancer effects require further elucidation.
  • * Key signaling pathways involving transcription factors like NF-kappa B and AP-1 are crucial for cell survival and proliferation.

Purpose of the Study:

  • * To investigate the time-dependent regulatory effects of quercetin on NF-kappa B and AP-1 transcription factors.
  • * To explore quercetin's impact on survival/proliferation pathways in HepG2 human hepatoma cells.
  • * To elucidate the role of these transcription factors in quercetin-induced cell death.

Main Methods:

  • * Treatment of HepG2 cells with quercetin (50 microM).
  • * Time-course analysis of NF-kappa B and AP-1 binding activities.
  • * Assessment of downstream signaling molecules including AKT, ERK, caspase-3, p38, and Bcl-2 family proteins.

Main Results:

  • * Quercetin induced a time-dependent inactivation of the NF-kappa B pathway, observed from 15 minutes onwards.
  • * A concurrent time-dependent activation of the AP-1/JNK pathway was observed, sustained up to 18 hours.
  • * These pathway modulations influenced cell death signals, including caspase-3 activation and Bcl-2 family protein imbalance, and regulated survival pathways (AKT, ERK).

Conclusions:

  • * NF-kappa B and AP-1 are critical regulators of survival/proliferation pathways influenced by quercetin.
  • * Sustained JNK/AP-1 activation and NF-kappa B inhibition by quercetin promote HepG2 cell death.
  • * Quercetin's anticarcinogenic effects are mediated through the modulation of these key transcription factors and associated signaling cascades.

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