A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines.

In light of the continuing need for effective anticancer agents, and the association of fruit and vegetable consumption with reduced cancer risk, edible plants are increasingly being considered as sources of anticancer drugs. Cranberry presscake (the material remaining after squeezing juice from the berries), when fed to mice bearing human breast tumor MDA-MB-435 cells, was shown previously to decrease the growth and metastasis of tumors. Therefore, further studies were undertaken to isolate the components of cranberry that contributed to this anticancer activity, and determine the mechanisms by which they inhibited proliferation.

A "combination oligonucleotide" antisense strategy to downregulate thymidylate synthase and decrease tumor cell growth and drug resistance.

Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell proliferation, and sensitize cells to TS-directed chemotherapeutic drugs.

Tumor growth inhibition in vivo and G2/M cell cycle arrest induced by antisense oligodeoxynucleotide targeting thymidylate synthase.

Chemotherapeutic agents targeting thymidylate synthase (TS) are effective against human tumors. Efficacy is limited by drug resistance, often mediated by TS overexpression. Treatment of HeLa cells in vitro with an antisense oligodeoxynucleotide (ODN 83) targeting human TS mRNA reduces TS mRNA and protein levels, inhibits cell proliferation, and sensitizes cells to TS-targeting drugs (Ferguson et al.

Metals and cellular signaling in mammalian cells.

A number of heavy metals are known to be essential for life, but most of these can also be toxic to cells under certain circumstances, or at elevated levels. Metals can directly induce gene expression through the actions of metal-responsive transcription factors. However, metals can also influence the response to non-metal extracellular signals.

Regional brain distribution of metallothionein, zinc and copper in toxic milk mutant and transgenic mice.

The regional distribution of metallothionein (MT), zinc and copper was measured in brains of transgenic MT-I overexpressor (MT-I*) mice, MT-I/MT-II gene knockout (MT-I/MT-II null) mice, and in brains of control C57BL/6J mice with normal MT expression. Toxic milk (tx) mutant mice with abnormally high MT and copper accumulation were also assessed. Although there were significant differences in MT levels (assessed by a cadmium-binding assay) in whole brain of MT-I/MT-II null and control mice (16.