A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis.

Cancer metastasis remains the most poorly understood process in cancer biology. It involves the degradation of extracellular matrix (ECM) proteins by a series of 'tumour-associated' proteases. Here we report the identification of a novel protease suppressor, NYD-SP8, which is located on human chromosome 19q13.2. NYD-SP8 encodes a 27 kD GPI-anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). Co-immunoprecipitation experiments showed that NYD-SP8 binds to uPA/uPAR complexes and interfere with active uPA production. Overexpression of NYD-SP8 results in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. These data demonstrate an important role of NYD-SP8 in regulating ECM degradation, providing a novel mechanism that modulates urokinase signalling in the suppression of cancer progression.

Natural inhibitors of DNA topoisomerase I with cytotoxicities.

DNA Topoisomerase I can cause DNA breaks and play a key role during cell proliferation and differentiation. It is an important target for anticancer agents. While screening for anticancer compounds, seven natural compounds, 1-7, showed potent cytotoxicities against a panel of ten cancer cell lines. Moreover, an inhibition assay demonstrated that they are also DNA topoisomerase I inhibitors, in which inhibitors 1-5 are new ones.

Chamobtusin A, a novel skeleton diterpenoid alkaloid from Chamaecyparis obtusa cv. tetragon.

The novel diterpenoid alkaloid chamobtusin A (1) was isolated from the branches and leaves of Chamaecyparis obtusa cv. tetragon. Its structure and relative stereochemistry were mainly determined by MS, 2D NMR, and X-ray methods. The methanol extracts, total alkaloids of C. obtusa cv. tetragon, and chamobtusin A were tested for their cytotoxicities against A549 and K562 human tumor cell lines.

A new abietane diterpene from Glyptostrobus pensilis.

A new abietane diterpene, glypensin A (1) and four known compounds, 12-acetoxy-ent-labda-8(17), 13E-dien-15-oic acid (2), quercetin 3-O-α-L-arabinofuranoside (3), quercetin 3-O-ß-D-galactopyranoside (4), ß-sitosterol (5) were isolated from the branches and leaves of Glyptostrobus pensilis (Staut.) Koch. Their structures were determined by MS, 1D- and 2D-NMR means. Compound 1 showed cytotoxicity on human chronic myeloid leukemia cell line K562 (IC(50) = 21.2µM).

Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications.

Anti-apoptotic activity of Bak Foong Pills and its ingredients on 6-hydroxydopamine-induced neurotoxicity in PC12 cells.

Bak Foong Pills (BFP), a traditional Chinese medicine used for centuries for the enhancement of women's health, was shown to display neuro-protective activity in the 1-methyl-4-phenyl-1,2,4,6,-tetrahydro-pyridine (MPTP)-induced mouse model in a previous study. In order to elucidate its mechanism of action, we investigated the anti-apoptotic properties of Bak Foong Pills and its main ingredients, including Panax ginseng, Angelica sinensis, Glycyrrhiza uralensis, and Ligusticum chuanxiong, in the 6-hydroxydopamine (6-OHDA)-treated PC12 cell model. The addition of the neurotoxin could cause significant cell death and reduction of cell proliferation, as shown in the results determined by MTT assay, nitric oxide (NO) measurement and flow cytometric propidium iodine (PI) staining analysis, while pre-treatment of PC12 cell with either BFP or its main ingredients prevented the toxicity to some degree. In addition, the neurotoxin caused an elevated activation of caspase-3, the key enzyme for activation of the cellular apoptotic cascade, whereas BFP or its main ingredients inhibited the activation of caspase-3. These results strongly indicate that BFP and its main ingredients may provide a useful therapeutic strategy for the treatment of neurodegenerative diseases, such as Parkinson's disease.