Journal
MOLECULAR CANCER THERAPEUTICS
Volume 9, Issue 8, Pages 2255-2264Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-10-0172
Keywords
-
Categories
Funding
- Flight Attendants Medical Research Institute (FAMRI
- Johns Hopkins CTSA Institute for Clinical and Translational Research [UL1RR025005]
- Sol Goldman Pancreatic Cancer Research Center
- Michael Rolfe Foundation for Pancreatic Cancer Research
- German Academic Exchange (DAAD)
- SignPath Pharmaceuticals, Inc
- [R01CA113669]
- [R01CA13767]
- [P01CA134292]
Ask authors/readers for more resources
Curcumin or diferuloylmethane is a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa). A large volume (several hundreds) of published reports has established the anticancer and chemopreventative properties of curcumin in preclinical models of every known major cancer type. Nevertheless, the clinical translation of curcumin has been significantly hampered due to its poor systemic bioavailability, which mandates that patients consume up to 8 to 10 g of the free drug orally each day to achieve detectable levels in circulation. We have engineered a polymeric nanoparticle encapsulated curcumin formulation (NanoCurc) that shows remarkably higher systemic bioavailability in plasma and tissues compared with free curcumin upon parenteral administration. In xenograft models of human pancreatic cancer established in athymic mice, administration of parenteral NanoCurc significantly inhibits primary tumor growth in both subcutaneous and orthotopic settings. The combination of parenteral NanoCurc with gemcitabine results in enhanced tumor growth inhibition versus either single agent, suggesting an additive therapeutic influence in vivo. Furthermore, this combination completely abrogates systemic metastases in orthotopic pancreatic cancer xenograft models. Tumor growth inhibition is accompanied by significant reduction in activation of nuclear factor-kappa B, as well as significant reduction in expression of matrix metalloproteinase-9 and cyclin D1, in xenografts treated with NanoCurc and gemcitabine. NanoCurc is a promising new formulation that is able to overcome a major impediment for the clinical translation of curcumin to cancer patients by improving systemic bioavailability, and by extension, therapeutic efficacy. Mol Cancer Ther; 9(8); 2255-64. (C) 2010 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available