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Imperatorin efficiently blocks TNF-α-mediated activation of ROS/PI3K/Akt/NF-κB pathway

Ke Si Wang1, Ying Lv1, Zhe Wang1

  • 1Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanbian, Jilin 133002, P.R. China.

Oncology Reports
|April 26, 2017
PubMed

Insights

Imperatorin, derived from Angelica dahurica, effectively reduces inflammation by inhibiting key pathways like NF-κB and PI3K/Akt. This natural compound shows promise in combating cancer-related inflammation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Inflammation is a key driver in cancer development and progression, particularly in cervical cancer.
  • Cervical cancer remains a significant global health issue for women worldwide.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of imperatorin, a compound from Angelica dahurica.
  • To elucidate the molecular mechanisms by which imperatorin modulates inflammatory responses in cancer cells.

Main Methods:

  • Utilized HeLa cells stimulated with tumor necrosis factor-alpha (TNF-α).
  • Assessed the impact of imperatorin on cytokine production and expression.
  • Analyzed key signal-transduction pathways including NF-κB and PI3K/Akt.
  • Measured reactive oxygen species (ROS) generation.

Main Results:

  • Imperatorin significantly inhibited TNF-α-induced expression of NF-κB target genes (COX-2, cyclin D1, MMP-9, VEGF, IL-6, Bcl-xL).
  • Imperatorin suppressed NF-κB activation by inhibiting IKKα/β and IκB phosphorylation, and NF-κB p65 nuclear translocation.
  • Imperatorin downregulated TNF-α-induced PI3K/Akt activation and inhibited ROS generation.

Conclusions:

  • Imperatorin exhibits potent anti-inflammatory properties against TNF-α stimulation in cancer cells.
  • The anti-inflammatory action of imperatorin is mediated through the inhibition of ROS-dependent PI3K/Akt/NF-κB signaling.
  • Imperatorin represents a potential therapeutic agent for managing inflammation in cancer.

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