The lower uptake rate http://www.selleckchem.com/products/arq-197.html may explain the low toxicity of curcumin for healthy cells. The wide spectrum of pharmacological properties of Inhibitors,Modulators,Libraries curcumin is attributed Inhibitors,Modulators,Libraries to its numerous Inhibitors,Modulators,Libraries effects on several targets including transcription factors, growth regula tors, adhesion molecules, apoptotic genes, angiogenesis regulators, and cellular signaling molecules. Curcu min exerts anti cancer activity mainly through blocking cell cycle progression and triggering tumor cell apoptosis. All three stages of carcinogenesis including initi ation, promotion and progression are suppressed by cur cumin. This is probably due to inhibition of the nuclear factor ��B, which plays a central role in regulat ing the expression of various genes involved in cell sur vival, apoptosis, carcinogenesis and inflammation.
This efficacy makes curcumin to a potential therapeutic target. Furthermore, curcumin affects various cell cycle proteins and checkpoints involving downregulation of some of the cyclins and cyclin dependent kinases, upregulation of cdk inhibitors, and inhibition of DNA syn thesis. However, the physiological response triggered by curcumin depends on the cell type, the concentration Inhibitors,Modulators,Libraries of curcumin and the time of treatment. For instance, curcumin treatment was reported to ar rest cell growth at G2M phase and induce apoptosis in human hepatoma cell line HepG2, whereas G0G1 as well as G1S phase arrests were reported for various other cell lines. Clinical use of curcumin remains very limited due to its extremely poor water solubility. and low bioavailability following oral administration.
Even when 10 12 gml of curcumin was administered orally in humans, curcumin levels in serum remained approximately at Inhibitors,Modulators,Libraries 50 ngml. Several studies demon strated that 10 50 uM curcumin in duces cell death primarily through apoptosis. However, the important question to be addressed is how to bring curcumin at these micromolar concentrations to the site of tumors while curcumin possesses such a low bioavailability. Addressing this problem, targeted and triggered drug delivery systems accompanied by nanoparticle technology have emerged as prominent so lutions. Likewise, this study introduces emulsomes as a promising nanocarrier system suitable for the deliv ery of curcumin. Emulsomes are biocompatible vesicular systems com prising of a solid fat core surrounded by phospholipid multi layers.
Due to the solid core, emul somes can entrap higher amounts AZD9291 astrazeneca of lipophilic drug compounds with a prolonged release time compared to emulsion formulations possessing a liquid core. Composed of fat and lipids, emulsomes are biocompat ible. Flavohemoglobin uti lizes O2 for NO detoxification and oxidize NO to harm less nitrate, which protect the bacteria from the toxic effect of NO. The significance of flavohemoglobin in NO protection has been shown using hmp deficient mutants that are more sensitive to NO and nitrosative stress.