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1.
J Cell Physiol ; 234(7): 10248-10259, 2019 07.
Article in English | MEDLINE | ID: mdl-30417547

ABSTRACT

High expression of ecto-5'-nucleotidase (CD73) has been reported in a number of epithelium origin malignancies. Here, we hypothesize that CD73 promotes hepatocellular carcinoma (HCC) growth and metastasis and that the effect is mediated by epithelial growth factor receptor (EGFR). HCC cells with different malignancies and Tissue microarrays of the tumor and peritumoral liver tissues from 30 independent patients were used to examine CD73 and EGFR expression. Then, MTT and Ki67 detection, together with cell adhesion, invasion, and migration assays were used to evaluate the effects of CD73 on cell growth and metastasis. The expression of EGFR in HCC cells was also tested after suppressing or overexpressing CD73. Lastly, tumor tissues from nude mice, which had been injected subcutaneously with HCC cells, were transplanted subcutaneously into CD73-/- and wild-type (WT) C57 mice. CD73 expression was higher in HCC cells with greater metastatic potentials and tumor tissues compared with low metastatic cells and peritumor tissues. CD73 and EGFR were coexpressed and positively correlated in tumor and peritumor liver tissues in HCC tissue microarrays. Up-regulationof CD73 by plasmid transfection or by pharmacological agents promoted EGFR expression in HCC cells, whereas suppression of CD73 inhibited these effects. The growth of transplanted tumor tissues was dramatically slower in CD73-/- mice than in WT type mice in the in vivo experiments. CD73 promotes HCC growth and metastasis and upregulated the expression of EGFR in HCC. Thus, CD73 and EGFR are potential targets in the treatment of HCC.


Subject(s)
5'-Nucleotidase/metabolism , Carcinoma, Hepatocellular/pathology , Cell Proliferation/physiology , Liver Neoplasms/pathology , Animals , Cell Adhesion/physiology , ErbB Receptors/metabolism , GPI-Linked Proteins/metabolism , Heterografts , Humans , Mice , Mice, Nude , Neoplasm Invasiveness/pathology
2.
Molecules ; 19(11): 17697-714, 2014 Oct 31.
Article in English | MEDLINE | ID: mdl-25365295

ABSTRACT

The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO), interleukin-1ß (IL-1ß), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). DATS and diallyl disulfide at 200 and 400 µM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases.


Subject(s)
Allium/chemistry , Allyl Compounds/pharmacology , Garlic/chemistry , Inflammation/drug therapy , Microglia/drug effects , Sulfur Compounds/pharmacology , Animals , Cell Line , Chemokine CCL2/metabolism , Cysteine/analogs & derivatives , Cysteine/pharmacology , Disulfides/pharmacology , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacology , Mice , Microglia/metabolism , NF-kappa B/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Nitric Oxide/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Sulfides/pharmacology , Tumor Necrosis Factor-alpha/metabolism
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