ABSTRACT
From fermented Taiwan foods, we have isolated numerous lactic acid bacteria (LAB) of plant origin and investigated their biological activities. This study aimed to investigate the immunomodulatory effect and mechanism of Lactococcus lactis A17 (A17), isolated from Taiwan fermented cabbage, on ovalbumin (OVA)-sensitized mice. Human peripheral blood mononuclear cells were used to verify immune responses of A17 by IFN-γ production. Live (A17-A) and heat-killed A17 (A17-H) were orally administered to OVA-sensitized BALB/c mice to investigate their effects on immunoglobulin (Ig) and cytokine production. The mRNA expression of Toll-like receptors (TLR) and nucleotide binding oligomerization domain (NOD)-like protein receptors in spleen cells was analyzed by real-time RT-PCR. Both live and heat-killed A17 modulate OVA-induced allergic effects. B-cell response was modulated by diminishing IgE production and raising OVA-specific IgG2a production, while T-cell response was modulated by increasing IFN-γ production and decreasing IL-4 production. The mRNA expression of NOD-1, NOD-2, and TLR-4 was down-regulated by A17 as well. This is the first report to describe a naïve Lactococcus lactis A17 strain as a promising candidate for prophylactic and therapeutic treatments of allergic diseases via oral administration. Our results suggest the ameliorative effects of A17 may be caused by modulating NOD-1 NOD-2, and TLR-4 expression.
ABSTRACT
A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M(3)N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M(3)N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M(3)N (4). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy.
Subject(s)
Antineoplastic Agents/chemical synthesis , Immunoconjugates/pharmacology , Prodrugs/chemical synthesis , beta-Lactamases/pharmacology , Antibodies, Neoplasm , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Division/drug effects , Cephalosporins , Drug Design , Drug Screening Assays, Antitumor , Drug Synergism , Humans , Hydrolysis/drug effects , Immunoconjugates/metabolism , Masoprocol , Prodrugs/metabolism , Prodrugs/pharmacology , Tumor Cells, Cultured , beta-Lactamases/immunology , beta-Lactamases/metabolismABSTRACT
7-(5'-Biotinylamidopropanoyl)paclitaxel was synthesised by chemical methods; its immunofluorescence assay and the cell uptake experiments were performed by use of human leukemia U937 cells. The results indicate that paclitaxel is arresting cell cycle at the G(2)M phase only.
