Apigenin Suppresses Bladder Cancer via the SIRT6-NCOA2-PPARα Axis

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Protein acetylation regulates tumor progression, but natural modulators are unclear.
• Dietary flavonoids like apigenin show potential in cancer therapy.
• Understanding molecular mechanisms is crucial for developing targeted treatments.

Purpose of the Study:

• To investigate the role of apigenin in bladder cancer progression.
• To elucidate the molecular mechanisms underlying apigenin's anti-cancer effects.
• To identify novel therapeutic targets in bladder cancer.

Main Methods:

• In vitro functional assays and dynamic xenograft models were used.
• An integrated multi-omics approach was applied.
• SIRT6-mediated deacetylation of Nuclear Receptor Coactivator 2 (NCOA2) was analyzed.

Main Results:

• Apigenin enhances SIRT6-mediated deacetylation of NCOA2 at specific lysine residues (780 and 785).
• This modification potentiates PPARα activity, reprograms cellular metabolism, and disrupts mitochondrial function.
• Reduced SIRT6 and elevated NCOA2 correlate with metastatic bladder cancer.

Conclusions:

• A novel SIRT6-NCOA2-PPARα signaling axis is identified in bladder cancer.
• This axis represents a metabolic vulnerability exploitable for therapeutic intervention.
• Apigenin's mechanism offers a potential strategy for bladder cancer treatment.