The anti-metastatic effect of Manuka honey on colonspheres enriched with cancer stem cells: how does it influence the epithelial-mesenchymal transition process, angiogenesis, and telomere length?

Danila Cianciosi; Tamara Yuliett Forbes-Hernández; Yasmany Armas Diaz; Maria Elexpuru Zabaleta; José L. Quiles; Maurizio Battino; Francesca Giampieri

Resumen:

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 colon spheres enriched with CSCs-like cells. In summary, it was observed that the treatment reduced migration ability by increasing the expression of E-cadherin through the downregulation of transcription factors Slug, Snail, and Twist. Additionally, it 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.