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The interaction between apigenin and PKM2 restrains progression of colorectal cancer

Jiangying Shi1, Xiaodan Ji1, Shuhua Shan1

  • 1Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.

The Journal of Nutritional Biochemistry
|August 19, 2023
PubMed

Insights

Apigenin, a natural compound, inhibits colorectal cancer (CRC) by targeting pyruvate kinase M2 (PKM2). It restricts cancer cell glycolysis and growth, showing promise as a safe therapeutic agent.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Apigenin, a flavonoid found in fruits and vegetables, exhibits potential anticancer properties with low toxicity.
  • The specific molecular targets and mechanisms of apigenin's anti-cancer effects remain largely unelucidated.
  • Understanding apigenin's direct targets is crucial for developing it as a therapeutic agent for tumors, particularly colorectal cancer (CRC).

Purpose of the Study:

  • To identify the direct molecular target of apigenin in colorectal cancer.
  • To determine the specific amino acid site involved in apigenin's interaction with its target.
  • To elucidate the mechanism by which apigenin exerts its anti-CRC effects.

Main Methods:

  • Correlation analysis between apigenin's anti-CRC activity and pyruvate kinase M2 (PKM2) expression in LS-174T cells with PKM2 knockdown.
  • Pull-down assays and MALDI-TOF/TOF analysis to identify direct interactions between apigenin and PKM2 in HCT-8 cells.
  • Site-directed mutagenesis and functional assays to confirm the role of lysine residue 433 (K433) in PKM2 binding to apigenin.

Main Results:

  • Apigenin's anti-CRC activity was positively correlated with PKM2 expression, with PKM2 knockdown reducing apigenin's efficacy.
  • Direct binding of apigenin to PKM2 was confirmed in HCT-8 cells.
  • Lysine residue 433 (K433) was identified as the key amino acid site for apigenin binding to PKM2.
  • Apigenin inhibited glycolysis in CRC cells by targeting PKM2 at the K433 site, leading to reduced cell proliferation and increased apoptosis.
  • Apigenin treatment significantly attenuated tumor growth in vivo without observable adverse effects.

Conclusions:

  • Apigenin directly targets PKM2 at the K433 residue to inhibit colorectal cancer.
  • Apigenin restricts cancer cell glycolysis, offering a novel therapeutic strategy for CRC.
  • Apigenin demonstrates significant anti-tumor efficacy with a favorable safety profile, positioning it as a promising PKM2 inhibitor for CRC prevention and treatment.
Keywords:
ApigeninColorectal cancer (CRC)GlycolysisPyruvate kinase M2 (PKM2)

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