# Pigmented Sorghum Phenolic Extracts Regulate the Expression of Cancer Development Pathway Genes in HT‐29 and Hypoxia‐Induced CCD 841 CoN Cells

## TL;DR

Pigmented sorghum extracts reduce cancer cell viability and modulate genes linked to cancer development and metabolism.

## Contribution

This study reveals how pigmented sorghum polyphenols affect key cancer-related genes in colorectal cancer cells.

## Key findings

- Sorghum extracts significantly reduced cancer cell viability at concentrations of 500 and 2000 μg/mL.
- BlackSs extract upregulated APC and TTN genes and downregulated GLUT-1 and HIF-1α/β in cancer cells.
- Processed RedBu2 also showed significant upregulation of the TTN gene.

## Abstract

Sorghum polyphenols have been shown to inhibit gastrointestinal cancer cell growth by inducing apoptosis and other pathways such as chronic inflammation. However, the impact of sorghum polyphenols on the most frequently mutated genes in the genome including mutation and instability and dysregulated cellular metabolism pathways is unknown. This study evaluated the gene and protein expression levels regulated by raw and fermented‐cooked (processed) sorghum phenolic extracts (BlackSs, BlackSb, and RedBu2) on HT‐29 and hypoxia‐induced CCD 841 CoN cells. Cancer cell viability was measured by Resazurin cytotoxicity assay and the gene and protein expression of APC, KRAS, TTN, HIF‐1α, HIF‐1β, and GLUT‐1 were measured using rtPCR and ELISA. Pigmented sorghum extracts showed a significant reduction in cancer cell viability at 500 and 2000 μg/mL after 12 and 24 h for raw samples but only after 24 h for processed. Treatment of HT‐29 cells with 500 μg/mL BlackSs sorghum extracts demonstrated a significant upregulation of APC at both 12 and 24 h time points, followed by TTN at the highest concentration and the KRAS gene after 24 h when compared to the control. BlackSb showed an increase in APC and TTN after 12 h of treatment. Furthermore, 500 μg/mL BlackSs significantly downregulated the expression of GLUT‐1 and decreased the expression of HIF‐1α, HIF‐1β at 2000 μg/mL. Interestingly, processed RedBu2 significantly upregulated TTN gene expression. Overall, the results from this study showed that sorghum polyphenols modulate key cancer development pathway‐associated genes in colorectal cancer cells, suggesting a potential chemopreventive role in inhibiting tumorigenesis.

A depiction of reconstituted red sorghum and black sorghum extract effects on HT‐29 and CCD 841 CoN cell cells at 500 and 2000 μg/mL for 12 and 24 h resulting in the decrease of cancer cell viability, modulation of mutation‐associated genes, and suppression of hypoxia and metabolic signaling.