Journal
CANCER LETTERS
Volume 364, Issue 2, Pages 135-141Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.05.005
Keywords
Colorectal liver metastases; Curcumin; Cancer stem cells; Combination therapy
Categories
Funding
- Hope Against Cancer, Leicester, UK
- Royal College of Surgeons (Eng)
- Bowel Disease Research Foundation
- Cancer Research UK [C325/A13101]
- Cancer Research UK
- Department of Health on an Experimental Cancer Medicine Centre [C325/A15575]
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In vitro and pre-clinical studies have suggested that addition of the diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of chemotherapy in models of colorectal cancer. However, the majority of evidence for this currently derives from established cell lines. Here, we utilised patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem cell (CSC) models. Combination of curcumin with FOLFOX chemotherapy was then assessed clinically in a phase I dose escalation study. Curcumin alone and in combination significantly reduced spheroid number in CRLM CSC models, and decreased the number of cells with high aldehyde dehydrogenase activity (ALDH(high)/CD133(-)). Addition of curcumin to oxaliplatin/5-FU enhanced anti-proliferative and pro-apoptotic effects in a proportion of patient-derived explants, whilst reducing expression of stem cell-associated markers ALDH and CD133. The phase I dose escalation study revealed curcumin to be a safe and tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses up to 2 grams daily. Curcumin may provide added benefit in subsets of patients when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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