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Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway

Byeong Hyeok Choi1, Chang Gun Kim, Yoongho Lim

  • 1Department of Biomedical Science and Technology, IBST, Konkuk University, Seoul 143-701, Republic of Korea.

Cancer Letters
|November 17, 2007
PubMed

Insights

Curcumin, a turmeric compound, reduces P-glycoprotein expression in drug-resistant cancer cells. This action may reverse multidrug resistance by inhibiting key cellular signaling pathways.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • Curcumin, derived from turmeric, exhibits anti-inflammatory and anti-carcinogenic properties.
  • P-glycoprotein (P-gp) expression, regulated by the mdr gene, is linked to multidrug resistance (MDR) in cancer.
  • Multidrug resistance poses a significant challenge in cancer chemotherapy.

Purpose of the Study:

  • To investigate the effect of curcumin on P-glycoprotein expression in multidrug-resistant cancer cells.
  • To identify the specific gene promoter region responsible for curcumin's effect on P-gp expression.
  • To explore the signaling pathways involved in curcumin-mediated suppression of P-gp.

Main Methods:

  • Utilized multidrug-resistant L1210/Adr cells.
  • Performed transfections with 5'-deleted constructs of the mdr1b gene promoter.
  • Analyzed the involvement of the PI3K/Akt/NF-kappa B signaling pathway.

Main Results:

  • Curcumin significantly down-regulates P-glycoprotein expression in L1210/Adr cells.
  • A proximal region of the mdr1b gene promoter (between -205 and +42) mediates this suppression.
  • Curcumin's action is associated with the inhibition of the PI3K/Akt/NF-kappa B signaling pathway.
  • Curcumin treatment reversed the multidrug resistance phenotype in L1210/Adr cells.

Conclusions:

  • Curcumin suppresses P-glycoprotein expression, a key factor in multidrug resistance.
  • The PI3K/Akt/NF-kappa B signaling pathway is implicated in curcumin's MDR-reversal effects.
  • Curcumin shows potential as a therapeutic agent to overcome multidrug resistance in cancer treatment.

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