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Title: Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metsastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy
Authors: James, Mark I.
Iwuji, Chinenye O. O.
Irving, Glen
Karmokar, Ankur
Higgins, Jennifer A.
Griffin-Teal, Nicola
Thomas, Anne
Greaves, Peter
Cai, Hong
Patel, Samita R.
Morgan, Bruno
Dennison, Ashley
Metcalf, Matthew
Garcea, Giuseppe
Lloyd, David M.
Berry, D. P.
Steward, William P.
Howells, Lynne M.
Brown, Karen
First Published: 12-May-2015
Publisher: Elsevier
Citation: Cancer Letters 364 (2015) 135–141
Abstract: 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 (ALDHhigh/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.
DOI Link: 10.1016/j.canlet.2015.05.005
ISSN: 0304-3835
eISSN: 1872-7980
Version: Published version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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