curcumin and Hematologic-Neoplasms

Despite considerable improvements in the tolerance and efficacy of novel chemotherapeutic agents, the mortality of hematological malignancies is still high due to therapy relapse, which is associated with bad prognosis. Dietary polyphenolic compounds are of growing interest as an alternative approach, especially in cancer treatment, as they have been proven to be safe and display strong antioxidant properties. Here, we provide evidence that both resveratrol and curcumin possess huge potential for application as both chemopreventive agents and anticancer drugs and might represent promising candidates for future treatment of leukemia. Both polyphenols are currently being tested in clinical trials. We describe the underlying mechanisms, but also focus on possible limitations and how they might be overcome in future clinical use--either by chemically synthesized derivatives or special formulations that improve bioavailability and pharmacokinetics.

Topics: Antioxidants; Apoptosis; Cell Cycle; Cell Proliferation; Clinical Trials as Topic; Curcumin; Diet; Hematologic Neoplasms; Humans; Molecular Structure; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Stilbenes

Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.. CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells.. Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and -19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 μg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63±0.23 μg/mL, 26.03 ± 1.5 μg/mL and 17.52 ± 0.22 μg/mL, respectively.. Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.

Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Drug Delivery Systems; Emulsions; Hematologic Neoplasms; Humans; Leukemia; Nanoparticles; Pharmaceutical Preparations; Solubility; Surface-Active Agents; Zebrafish