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Published on: June 30, 2023
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.
Abstract:
Kaempferol has been reported to reduce the risk of ovarian cancer, but the mechanism is not completely understood. In this study, we tend to expand our understanding on how kaempferol regulates VEGF expression and angiogenesis in ovarian cancer cells. We timed VEGF secretion, and studied in-vitro angiogenesis by kaempferol treatment. Gene expression was examined by qRT-PCR, ELISA, Western Blotting, or luciferase assay, and pathways were examined by manipulating genetic components with plasmid or siRNA transfection. It was found that kaempferol time-dependently inhibited VEGF secretion, and suppressed in-vitro angiogenesis. Kaempferol down-regulated ERK phosphorelation as well as NFκB and cMyc expression, but promoted p21 expression. Examination of relationship between these genes suggested a novel ERK-NFκB-cMyc-p21-VEGF pathway, which accounts for kaempferol's angioprevention effects in ovarian cancer cells. This data supplements our comprehension of the mechanisms behind kaempferol's biological influence in ovarian cancer cells, and better characterized kaempferol toward chemoprevention.
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.
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