# Investigating the Molecular Mechanisms of the Anticancer Effects of Eugenol and Cinnamaldehyde Against Colorectal Cancer (CRC) Cells In Vitro

## TL;DR

This study explores how eugenol and cinnamaldehyde fight colorectal cancer cells in the lab, showing they kill cancer cells and may help in cancer treatment.

## Contribution

The study reveals the distinct molecular mechanisms of eugenol and cinnamaldehyde in targeting colorectal cancer cells.

## Key findings

- Eugenol and cinnamaldehyde selectively kill colorectal cancer cells without harming normal colon cells.
- Eugenol causes major changes in gene activity, while cinnamaldehyde reduces inflammation in cancer cells.
- Both compounds show potential as natural anticancer agents, possibly enhancing chemotherapy.

## Abstract

Colorectal cancer is one of the leading causes of cancer-associated mortality, and multifactorial resistance remains one of the main challenges in its treatment. Essential oils and their main compounds show interesting anticancer properties, but their mechanism of action is yet to be defined. This study aims to assess the cytotoxic effects of eugenol (EU) and cinnamaldehyde (CN) on colorectal cancer (CRC) cells, highlighting possible mechanisms of action. These compounds were tested on normal immortalized colonocytes (NCM-460) and two CRC cell lines: Caco-2, a human colon epithelial adenocarcinoma cell line, and SW-620, colon cancer cells derived from a lymph node metastatic site. The efficacy of EU and CN was evaluated through CellTiter-Glo® and clonogenic assays and by determining proinflammatory cytokine secretion. Transcriptome analysis was used to identify possible pathways affected by EU and CN treatments. The results confirmed that EU and CN were selectively cytotoxic and pro-apoptotic against CRC cells, with different putative mechanisms. While EU drove cytotoxicity through robust transcriptional remodeling, CN yielded a stronger anti-inflammatory action. We confirmed that EU and CN are promising natural candidates in CRC prevention and treatment, even in association with chemotherapeutic drugs.