An old spice with new tricks: Curcumin targets adenoma and colorectal cancer stem-like cells associated with poor survival outcomes

作者：Sam Khan, Ankur Karmokar, Lynne Howells, Robert G. Britton, Emma Parrott, Raquel Palacios-Gallego, Cristina Tufarelli, Hong Cai, Jennifer Higgins, Nicolas Sylvius, Kevin West, Angus McGregor, David T. Moore, Selena G. Burgess, Mark W. Richards, Anja Winter, Zahirah Sidat, Nalini Foreman, Sanne ten Hoorn, Louis Vermeulen, Baljit Singh, David Hemingway, Michael Norwood, Andrew M. Miller, Kirsten Boyle, Carmen Ho, Muhammad Imran Aslam, Richard Bayliss, Abdolrahman S. Nateri, Alessandro Rufini, Andreas Gescher, Anne Thomas, William P. Steward, Karen Brown · 发表于：Cancer Letters · 年份：2025 · DOI：10.1016/j.canlet.2025.217885 · 被引用次数：6 · 研究领域：Cancer Cells and Metastasis、Cancer-related Molecular Pathways、Genetic factors in colorectal cancer

The cost of cancer care globally is unsustainable and strategies to reduce the mounting burden of cancer are urgently needed. One approach is the use of preventive therapies to reduce cancer risk; dietary-derived compounds with good safety profiles represent a promising source of potential candidates but translating encouraging preclinical data to successful trials presents significant challenges. Development of curcumin, from the spice turmeric, as a preventive therapy for colorectal cancer (CRC) is hindered by poor understanding of its mechanism of action. Using patient derived xenografts and ex-vivo 3D-models exposed to clinically achievable curcumin concentrations, we found that it targets proliferating cancer stem-like cells (CSCs) within premalignant adenoma and early-stage cancer tissues, with broad spectrum activity across all molecular subtypes. Transcriptomics analysis revealed that curcumin pushes CSCs towards differentiation over self-renewal, thereby inhibiting tumour development. Evidence suggests these effects involve direct protein binding of curcumin to NANOG, a master regulator of CRC CSCs, and impairment of its transcriptional activity via direct interference with NANOG-DNA binding. Furthermore, curcumin decreased the proportion of proliferating CSCs, defined by NANOG/Ki67 co-expression in patient derived explants and individuals with tumours containing a small fraction of these cells had greatly improved progression-free survival compared to those in the h...