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Britannin induces apoptosis through AKT-FOXO1 pathway in human pancreatic cancer cells

Marzieh Moeinifard1, Zuhair Mohammad Hassan2, Faranak Fallahian3

  • 1Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 20, 2017
PubMed

Insights

Britannin induces cancer cell death by promoting apoptosis in human pancreatic cancer cells. This natural compound triggers programmed cell death via reactive oxygen species and the AKT-FOXO1 pathway, offering potential as a pancreatic cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Inducing apoptosis in cancer cells is a key strategy in cancer therapy.
  • Pancreatic cancer remains a significant health challenge with limited effective treatments.

Purpose of the Study:

  • To investigate the anticancer effects of Britannin in human pancreatic cancer cells.
  • To elucidate the molecular mechanisms underlying Britannin-induced apoptosis.

Main Methods:

  • Annexin V-FITC/PI staining, Hoechst 33258 staining, and caspase-3 activity assays.
  • Western blot and Real-time PCR to analyze gene and protein expression (BCL-2, BAX, AKT, FOXO1, BIM).
  • Measurement of reactive oxygen species (ROS) generation.

Main Results:

  • Britannin induced apoptosis in AsPC-1 and Panc-1 pancreatic cancer cells.
  • Britannin modulated apoptosis-related proteins, decreasing BCL-2 and increasing BAX expression.
  • Britannin increased ROS production, decreased phosphorylated AKT, and promoted FOXO1 nuclear accumulation, leading to BIM upregulation.

Conclusions:

  • Britannin induces apoptosis in pancreatic cancer cells through the mitochondrial pathway.
  • The mechanism involves ROS generation and modulation of the AKT-FOXO1 signaling axis.
  • Britannin shows potential as an anticancer agent for pancreatic cancer treatment.
Keywords:
ApoptosisBritanninFOXO1Pancreatic cancer

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