ABSTRACT
Niclosamide, an oral antihelminthic drug, has been used to treat tapeworm infection for about 50 years. Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs. Recently, several groups have independently discovered that niclosamide is also active against cancer cells, but its precise mechanism of antitumor action is not fully understood. Evidence supports that niclosamide targets multiple signaling pathways (NF-κB, Wnt/β-catenin, Notch, ROS, mTORC1, and Stat3), most of which are closely involved with cancer stem cells. The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed. A method for synthesizing a phosphate pro-drug of niclosamide is provided. Given its potential antitumor activity, clinical trials for niclosamide and its derivatives are warranted for cancer treatment.
Subject(s)
Animals , Humans , Antineoplastic Agents , Pharmacokinetics , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Mechanistic Target of Rapamycin Complex 1 , Multiprotein Complexes , Metabolism , NF-kappa B , Metabolism , Neoplasm Metastasis , Neoplasms , Metabolism , Pathology , Neoplastic Stem Cells , Niclosamide , Pharmacokinetics , Pharmacology , Reactive Oxygen Species , Metabolism , Receptors, Notch , Metabolism , STAT3 Transcription Factor , Metabolism , Signal Transduction , TOR Serine-Threonine Kinases , Metabolism , Wnt Signaling PathwayABSTRACT
<p><b>BACKGROUND</b>Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability.</p><p><b>METHODS</b>Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propagate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line's ability to directly differentiate into pancreatic and hepatic cells.</p><p><b>RESULTS</b>We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line.</p><p><b>CONCLUSIONS</b>This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.</p>
Subject(s)
Humans , Cell Differentiation , Physiology , Cell Line , Embryonic Stem Cells , Cell Biology , Hepatocytes , Cell Biology , Metabolism , Karyotyping , Pancrelipase , Metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Stromal cell derived factor (SDF), expressing on bone marrow stromal cells is a CXC-type chemokine, which specifically chemoattracts hematopoietic stem cells (HSCs) expressing CXCR4. SDF plays important roles in homing and mobilizing of HSCs. In this paper the regulatory mechanism of SDF/CXCR4 in the HSC migration process is mainly reviewed.