Epigenetic Remodeling of Regulatory Regions by Indicaxanthin Suggests a Shift in Cell Identity Programs in Colorectal...

Area of Science:

• Epigenetics and Nutraceuticals
• Molecular Oncology
• Cancer Cell Biology

Background:

• Aberrant DNA methylation is a key driver in colorectal cancer (CRC) progression.
• Indicaxanthin (IND), a betalain pigment from Opuntia ficus indica, exhibits antiproliferative effects in CRC models.
• The epigenetic impact of IND on CRC cells remains largely unexplored.

Purpose of the Study:

• To investigate the effects of Indicaxanthin (IND) on the DNA methylome of colorectal cancer (CRC) cells.
• To identify specific genes and genomic regions affected by IND-induced methylation changes.
• To explore the functional consequences of these epigenetic alterations on CRC cell fate and metabolism.

Main Methods:

• Utilized Reduced Representation Bisulfite Sequencing (RRBS) to analyze the methylome of Caco-2 cells treated with IND.
• Performed functional enrichment analysis to identify affected biological pathways.
• Investigated changes in transcription factor targets and repetitive elements.

Main Results:

• IND induced a global hypermethylation profile in CRC cells, particularly at gene promoters and CpG islands.
• Hypermethylation affected protein-coding genes and transcription factors (e.g., PAX5, TFAP4) at active enhancers.
• IND modulated methylation of Alu elements and rDNA loci, suggesting impacts on cell identity, plasticity, and ribosomal biogenesis.

Conclusions:

• Indicaxanthin (IND) possesses significant epigenetic remodeling potential in colorectal cancer (CRC) cells.
• IND-induced methylation changes suggest a modulation of cell fate, potentially involving transdifferentiation processes.
• The findings highlight IND's potential role in altering cell metabolism and offer a basis for its therapeutic exploration in CRC.