Flavone induces changes in intermediary metabolism that prevent microadenoma formation in colonic tissue of...

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
• There is a critical need for novel therapeutics and adjuvants to combat CRC.
• Secondary plant compounds are being investigated for their potential anti-cancer properties.

Purpose of the Study:

• To investigate the effect of the plant compound flavone on the development of colorectal aberrant crypt foci and microadenomas in a mouse model.
• To elucidate the molecular mechanisms underlying flavone's potential chemopreventive effects.

Main Methods:

• Aberrant crypt foci and microadenoma development were induced in C57BL/6J mice using 1,2-dimethylhydrazine.
• Flavone was administered via gavage at 400 mg/kg body weight for 4 weeks post-induction.
• Proteome analysis (2-DE, mass spectrometry) and transcriptome analysis (Gene Chip expression array) were performed on colonocytes.

Main Results:

• Flavone treatment significantly increased apoptosis and reduced proliferation and aberrant crypt formation.
• Flavone completely suppressed the development of microadenomas.
• Proteomic and transcriptomic analyses revealed downregulation of the tricarboxylic acid cycle and increased FADH(2) production via fatty acid beta-oxidation.
• Increased expression of solute transporters suggested enhanced substrate supply for energy production independent of the tricarboxylic acid cycle.

Conclusions:

• Flavone demonstrates significant chemopreventive effects against colorectal cancer development in mice.
• Changes in intermediary metabolism proteins and their encoding mRNAs are associated with flavone-induced apoptosis and microadenoma prevention.
• Flavone's mechanism involves altering cellular energy metabolism and promoting programmed cell death in transformed colonocytes.