Kaempferol inhibits VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway

Haitao Luo1, Gary O Rankin, Noelle Juliano

  • 1Natural Science Division, Alderson-Broaddus College, Philippi, WV, USA.

Food Chemistry
|September 20, 2011
PubMed

Insights

Kaempferol inhibits ovarian cancer cell growth by suppressing angiogenesis. This study reveals a novel pathway involving ERK, NFκB, cMyc, and p21, explaining kaempferol

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Kaempferol shows potential in reducing ovarian cancer risk.
  • The precise mechanisms underlying kaempferol's effects on ovarian cancer remain unclear.

Purpose of the Study:

  • To elucidate how kaempferol regulates Vascular Endothelial Growth Factor (VEGF) expression and angiogenesis in ovarian cancer cells.
  • To identify the molecular pathways involved in kaempferol's anti-angiogenic effects.

Main Methods:

  • Investigated VEGF secretion and in-vitro angiogenesis upon kaempferol treatment.
  • Utilized quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), ELISA, Western Blotting, and luciferase assays for gene expression analysis.
  • Employed plasmid and siRNA transfection to manipulate genetic components and examine pathway involvement.

Main Results:

  • Kaempferol demonstrated time-dependent inhibition of VEGF secretion and suppressed in-vitro angiogenesis.
  • Down-regulated Extracellular signal-Regulated Kinase (ERK) phosphorylation, Nuclear Factor kappa B (NFκB), and c-Myc expression.
  • Promoted p21 expression, suggesting a role in cell cycle regulation.

Conclusions:

  • A novel signaling pathway (ERK-NFκB-cMyc-p21-VEGF) was identified, mediating kaempferol's angioprevention effects in ovarian cancer.
  • This pathway provides a deeper understanding of kaempferol's biological activity in ovarian cancer.
  • The findings support kaempferol's potential as a chemopreventive agent against ovarian cancer.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...