| The synthetic triterpenoid CDDO-Imidazolide suppresses experimental liver metastasis. | |
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MedLine Citation:
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PMID: 21234655 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Survival following diagnosis of liver metastasis remains poor and improved treatment strategies to combat liver metastases are needed. Synthetic triterpenoids, including 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Imidazolide or CDDO-Im), have been shown to inhibit primary tumor growth and lung metastasis in experimental models. Oral administration of CDDO-Im results in relatively high liver concentrations, suggesting that CDDO-Im may provide an approach to treatment of liver metastases. Here we assessed the effect of CDDO-Im on liver metastasis, using B16F1 (mouse melanoma) and HT-29 (human colon carcinoma) cells. In vitro, nanomolar concentrations of CDDO-Im arrested proliferation or induced cell death in both cell lines. In vivo, cells were injected via a surgically exposed mesenteric vein to target cells to the liver of mice. Mice were then treated with CDDO-Im (800 mg/kg diet) or vehicle control. Livers were removed at endpoint and metastatic burden was quantified by standard histology. In addition, a novel whole liver magnetic resonance imaging (MRI) technique was used to assess the effect of CDDO-Im on growing metastases as well as on non-dividing, solitary cancer cells present in the same livers. CDDO-Im treatment significantly decreased liver metastasis burden in both HT-29 (n = 8 treated, 10 control) and B16F1 (n = 15 treated, 16 control) injected mice (>60%, P < 0.05), but did not reduce the numbers of solitary B16F1 cancer cells (hypo-intensity) in the same livers (P = 0.9). This study demonstrates that CDDO-Im may be useful for the treatment metastatic liver disease as it successfully inhibits growth of actively proliferating liver metastases. |
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Authors:
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Jason L Townson; Ian C Macdonald; Karen T Liby; Lisa Mackenzie; David W Dales; Benjamin D Hedley; Paula J Foster; Michael B Sporn; Ann F Chambers |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-15 |
Journal Detail:
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Title: Clinical & experimental metastasis Volume: - ISSN: 1573-7276 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8409970 Medline TA: Clin Exp Metastasis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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London Regional Cancer Program, 790 Commissioners Road East, Office A4-903B, London, ON, N6A 4L6, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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