carbocyanines and epigallocatechin-gallate

The human telomerase reverse transcriptase catalytic subunit (hTERT) is the rate-limiting subunit of the telomerase holoenzyme. Down-regulating the expression of hTERT mRNA by antisense oligonucleotides would reduce the expression of hTERT, inhibit telomerase activity, and impair the growth of cancer cells in vitro. In this work, we propose a locked nucleic acid-functionalized gold nanoparticle flare probe (AuNP-probe). After transferring these probes into cells by endocytosis of the gold nanoparticles, the binding process of the antisense locked nucleic acid with hTERT mRNA along with gene regulation can be visualized by fluorescence recovery of flare-sequences. A significant decline in hTERT mRNA levels and the hTERT content occurred in cancer cells after treatment with the AuNP-probes, and only approximately 25% of the original level of hTERT mRNA remained after 72 h. AuNP-probe treated cancer cells were arrested in the G1 phase of the cell cycle and underwent apoptosis; cell viability decreased obviously compared with that of telomerase-negative normal cells.

Topics: Antineoplastic Agents; Apoptosis; Carbocyanines; Catechin; Cell Line, Tumor; Cell Survival; DNA; Down-Regulation; Enzyme Inhibitors; Fluorescence; Fluorescent Dyes; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Gold; Humans; Metal Nanoparticles; Microscopy, Confocal; Microscopy, Fluorescence; Nucleic Acid Hybridization; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Telomerase; Time Factors

Microglial activation is believed to play a pivotal role in the selective neuronal injury associated with several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down-regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG exerted significant protection against microglial activation-induced neuronal injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of microglial activation and thus is a useful candidate for a therapeutic approach to alleviating microglia-mediated dopaminergic neuronal injury in PD.

Topics: Analysis of Variance; Animals; Animals, Newborn; Antioxidants; Blotting, Western; Carbocyanines; Catechin; Cell Count; Cells, Cultured; Culture Media, Conditioned; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Lipopolysaccharides; Microglia; Microtubule-Associated Proteins; Neuroblastoma; Neurons; Nitric Oxide; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tetrazolium Salts; Thiazoles; Time Factors; Tumor Necrosis Factor-alpha; Tyrosine 3-Monooxygenase