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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：

: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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

James MI,Iwuji C,Irving G,Karmokar A,Higgins JA,Griffin-Teal N,Thomas A,Greaves P,Cai H,Patel SR,Morgan B,Dennison A,Metcalfe M,Garcea G,Lloyd DM,Berry DP,Steward WP,Howells LM,Brown K

doi

10.1016/j.canlet.2015.05.005

subject

Has Abstract

pub_date

2015-08-10 00:00:00

pages

135-41

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(15)00326-2

journal_volume

364

pub_type

杂志文章

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