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

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 highest quartile for expression. The use of curcumin to minimise this cellular population may yield significant benefit and its clinical evaluation is warranted. Overall, this study provides crucial mechanistic insight, identifying patient populations likely to benefit from curcumin for prevention of sporadic CRC and theragnostic biomarkers for assessing efficacy.

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Publication Details

Journal
Cancer Letters
Published
2025-06-19
DOI
https://doi.org/10.1016/j.canlet.2025.217885
Citations
4
Primary Topic
Cancer Cells and Metastasis
Type
article
Field-Weighted Citation Impact
4.18

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article

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

Nalini Foreman, Zahirah Sidat, Hong Cai, Ankur Karmokar et al.
4 citations
Cancer Letters
Cancer Cells and Metastasis
4.18
article

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

Nalini Foreman, Zahirah Sidat, Hong Cai, Ankur Karmokar, Sam Khan, Nicolas Sylvius, Lynne Howells, Selena G. Burgess, Mark W. Richards, Sanne ten Hoorn, Louis Vermeulen, Robert G. Britton, Richard Bayliss, David T. Moore, Karen Brown, Michael Norwood, Anne Thomas, Raquel Palacios-Gallego, Anja Winter, Baljit Singh, Kirsten Boyle, Cristina Tufarelli, Alessandro Rufini, Abdolrahman S. Nateri, Angus McGregor, Muhammad Imran Aslam, Andrew M. Miller, Andreas Gescher, William P. Steward, Kevin West, David Hemingway, Carmen Ho, Jennifer Higgins, Emma Parrott
article en
4 citations

Abstract

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 highest quartile for expression. The use of curcumin to minimise this cellular population may yield significant benefit and its clinical evaluation is warranted. Overall, this study provides crucial mechanistic insight, identifying patient populations likely to benefit from curcumin for prevention of sporadic CRC and theragnostic biomarkers for assessing efficacy.

Cancer LettersVol. 629
University of Leeds (GB), University of Nottingham (GB), University of Leicester (GB), University of Milan (IT), University Hospitals of Leicester NHS Trust (GB), University Hospitals Coventry and Warwickshire NHS Trust (GB), Oncode Institute (NL), CRUK Lung Cancer Centre of Excellence (GB), NIHR Leicester Biomedical Research Centre (GB), University College London (GB), Keele University (GB)
Wellcome Trust, Hope Against Cancer, Cancer Research UK, National Institute for Health and Care Research, University of Leicester, Medical Research Council, NIHR Leicester Biomedical Research Centre
No poverty
Openalex Percentile: Top 5%
Cancer Cells and Metastasis
4.18
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