Curcumin compositions and uses thereof

[0078]Pharmaceutical formulations prepared according to embodiments of the invention improve bioavailability of curcumin. For these examples, curcumin (95%) was purchased from Acros Organics. Tetrahydrocurcumin (THC) was prepared according to a published procedure (Ohtsu, et al., J. Med. Chem., 2002, 45(23), 5037-5042). The internal standard OSU-Arg was obtained from National Cancer Institute (Bethesda, Md., USA). Analytical HPLC grade methanol, acetonitrile, ethyl acetate and formic acid were purchased from Fisher Scientific (Pittsburgh, Pa., USA). Heparin-treated and EDTA-treated mouse plasma were purchased from Harlan Bioproducts (Indianapolis, Ind., USA). The phosphate buffer saline (PBS, pH 7.4) was purchased from Sigma-Aldrich (St. Louis, Mo., USA). All chemicals and reagents were used as received. An E-pure water purification system (Barnstead, Dubuque, Iowa) was used to obtain HPLC grade water (>18 mΩ).

[0079]The LC-MS system used consisted of a Finnigan TSQ Quantum EMR Triple Q

[0113]Curcumin formulations according to embodiments of the invention has anti-tumor activity. For these studies, the curcumin gel formulation was tested in a breast cancer model using MDA-MB-231 breast cancer cell engrafted nude mice. Female athymic nu / nu mice (4-6 weeks old, 18-22 g) were obtained from Charles River Laboratory (Wilmington, Mass.) and acclimated for 1 week in a pathogen-free enclosure before start of study. Animals were given sterile rodent chow and water ad libitum and were housed in sterile filter-top cages with 12 hour light / dark cycles. All experiments were conducted in accordance with the guidelines of the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). MDA-MB-231 cells (5×106 cells per mouse) were suspended with cell culture medium, and subcutaneously implanted into the right flank of the athymic nu / nu mice. When tumors were grown between 100 to 200 mm3, treatments were initiated. Mice were randomly assigned i

[0116]Abnormal DNA methylation has been observed in some types of cancers. As such, we evaluated the effect of the curcumin formulations according to embodiments of the invention on DNA methylation.

[0117]Materials: Decitabine (DAC) was obtained from the National Cancer Institute and used without further purification. Curcumin, methanol, acetonitrile (HPLC grade), ammonium formate, ammonium acetate, ammonium bicarbonate, 5-methyl-2-deoxycytidine (5mdC), 2-deoxycytidine (2dC), 2-deoxyguanosine (2dG), nucleophosphatase (NP1), snake venom phosphatase (SVP), and alkaline phosphatase (AP), deoxynucleotide triphosphate (2.5 mM), AmpliTaqGold polymerase and 10×PCR buffer were purchased from Sigma-Aldrich (St. Louis, Mo.). The primers for amplification of p15INK4B and its bisulfite-converted promoter region, p21, DNMT1, DNMT3a and DNMT3b, and Sp1 binding promoter region in DNMT1 were purchased from either Sigma-Aldrich (St. Louis, Mo.) or Integrated DNA Technology (IDT, Coralville, Iowa). M. Ss