1 research outputs found
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
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