Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial–mesenchymal transition, angiogenesis and telomere length

Abstract

Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial–mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial–mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc – demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.