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Results show that the nuclear gene ATPA. encoding the alpha-subunit of the mammalian mitochondrial F(sib)1F(sub)o ATP synthase complex, is regulated by a multifunctional binding site to which the transcriptional factors, the orphan nuclear factor COUP-TFII-1 and an upstream stimulatory factor USF2, bind and exert their antagonistic effects.

Focuses on the use of Celecoxib, a nonsteroidal anti-inflammatory drug and cyclooxygenase-2 inhibitor for the treatment of osteoarthritis and rheumatoid arthritis. Sulfonamide structural component of Celecoxib; Lower risks of severe gastrointestinal and platelet effects of Celecoxib; Other applications of Celecoxib. INSET: Formulary considerations.

The goal of this study was to develop a peptide which could use the toxic effects of amyloid, a substance which is the hallmark of over 25 known human diseases, to selectively kill cancer cells. Here we demonstrate that two separate amyloid-forming hexapeptides, one from the microtubule associated protein Tau involved in formation of paired helical filaments of Alzheimer's disease, and the other an amyloid forming sequence from apolipoprotein A 1 , when conjugated to a cell penetrating peptide (CPP) sequence, form toxic oligomers which are stable for up to 14 h and able to enter cells by a combination of endocytosis and transduction. The amyloid peptide conjugates showed selective cytotoxicity to breast cancer, neuroblastoma and cervical cancer cells in culture compared to normal cells. Fluorescence imaging experiments showed the CPP-amyloid peptide oligomers formed intracellular fibrous amyloid, visible in the endosomes/lysosomes, cytosol and nucleus with thioflavin S (ThS) staining. Further experiments with rhodamine-conjugated Dextran, propidium iodide (PI), and acridine orange (AO) suggested the mechanism of cell death was the permeability of the lysosomal membrane brought about by the formation of amyloid pores. Cytotoxicity could be abrogated by inhibitors of lysosomal hydrolases, consistent with a model where lysosomal hydrolases leak into the cytosol and induce cytotoxicity in subsequent downstream steps. Taken together, our data suggest that CPP-amyloid peptide conjugates show potential as a new class of anti-cancer peptides (ACPs).