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Article Publish Status: FREE
Abstract Title:

Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy.

Abstract Source:

Cancer Lett. 2015 Aug 10 ;364(2):135-41. Epub 2015 May 12. PMID: 25979230

Abstract Author(s):

Mark I James, Chinenye Iwuji, Glen Irving, Ankur Karmokar, Jennifer A Higgins, Nicola Griffin-Teal, Anne Thomas, Peter Greaves, Hong Cai, Samita R Patel, Bruno Morgan, Ashley Dennison, Matthew Metcalfe, Giuseppe Garcea, David M Lloyd, David P Berry, William P Steward, Lynne M Howells, Karen Brown

Article Affiliation:

Mark I James

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 (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.

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Sayer Ji
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