Kaempferol Reverses Aerobic Glycolysis via miR-339-5p-Mediated PKM Alternative Splicing in Colon Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Colon cancer presents limited therapeutic options with significant adverse effects.
• There is an urgent need for novel, effective colon cancer drugs.
• Kaempferol, a natural flavonoid, shows potential anti-cancer properties.

Purpose of the Study:

• To investigate the anti-cancer effects of kaempferol on human colon cancer cells.
• To elucidate the molecular mechanisms underlying kaempferol's anti-tumor activity.
• To explore kaempferol's impact on cellular metabolism and key regulatory pathways.

Main Methods:

• Cell proliferation assays (IC50 determination) on HCT116 and DLD1 cells.
• Cell cycle analysis and apoptosis induction studies.
• Assessment of glucose consumption, lactic acid, and ATP production.
• Analysis of miR-339-5p expression and its targets (hnRNPA1, PTBP1).
• Investigation of pyruvate kinase isoforms (PKM2 and PKM1) regulation.

Main Results:

• Kaempferol inhibited colon cancer cell proliferation in a dose-dependent manner.
• Kaempferol treatment induced cell cycle arrest at G1 phase and promoted apoptosis.
• Kaempferol impaired aerobic glycolysis by reducing glucose uptake and ATP production.
• Kaempferol upregulated miR-339-5p, targeting hnRNPA1 and PTBP1.
• This modulation led to decreased PKM2 and increased PKM1 expression.

Conclusions:

• Kaempferol exhibits significant anti-proliferative and anti-glycolytic effects on colon cancer cells.
• The anti-tumor activity of kaempferol is mediated through the miR-339-5p/hnRNPA1/PTBP1/PKM axis.
• Kaempferol represents a potential therapeutic agent for colon cancer, offering a new mechanistic understanding.