Bioactivity Evaluation of a Novel Formulated Curcumin.

Curcumin has been used as a traditional medicine and/or functional food in several cultures because of its health benefits including anticancer properties. However, poor oral bioavailability of curcumin has limited its oral usage as a food supplement and medical food. Here we formulated curcumin pellets using a solid dispersion technique. The pellets had the advantages of reduced particle size, improved water solubility, and particle porosity. This pellet form led to an improvement in curcumin's oral bioavailability. Additionally, we used the C-Map and Library of Integrated Network-Based Cellular Signatures (LINCS) Unified Environment (CLUE) gene expression database to determine the potential biological functions of formulated curcumin. The results indicated that, similar to conventional curcumin, the formulated curcumin acted as an NF-κB pathway inhibitor. Moreover, ConsensusPathDB database analysis was used to predict possible targets and it revealed that both forms of curcumin exhibit similar biological functions, including apoptosis. Biochemical characterization revealed that both the forms indeed induced apoptosis of hepatocellular carcinoma (HCC) cell lines. We concluded that the formulated curcumin increases the oral bioavailability in animals, and, as expected, retains characteristics similar to conventional curcumin at the cellular level. Our screening platform using big data not only confirms that both the forms of curcumin have similar mechanisms but also predicts the novel mechanism of the formulated curcumin.

Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction.

We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC. 3y also induced stronger apoptosis and autophagy. Addition of curcumin enhanced 3y-induced cytotoxicity by further induction of autophagy. Using gene expression signatures of 3y to query Connectivity Map, a glycogen synthase kinase-3 inhibitor (AR-A014418) was predicted to display similar molecular action of 3y. Experiments further demonstrate that AR-A014418 acted like 3y, and vice versa. Overall, our data suggest the chemotherapeutic potential of 3y on HCC.