Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper

Photoluminescence anaysis of Teflon bulk and Teflon-like films grown by ion beam sputtering

We have investigated the photoluminescence of Teflon-like films obtained by ion-beam sputtering. We show that Teflon material used for the target contains pi-C bonds. The sputtering increases the number of these bonds inside the films. By changing some experimental parameters it is possible to control centres of radiative recombination obtaining also a Teflon film without this centres

Methylxanthine, alcohol-free diet and fibrocystic breast disease : a factorial clinical trial

A controlled clinical trial was conducted in Milan, Italy to analyze the effects of methylxanthine (MTX) and alcohol abstention on signs and symptoms of fibrocystic breast disease. A total of 192 women with a clinical and thermographic diagnosis of fibrocystic breast disease were randomly assigned to four groups on the basis of two-by-two factorial design: (1) abstention from MTX-containing beverages, (2) abstention from alcohol, (3) abstention from MTX and alcohol, and (4) no dietary advice. Of these, 162 (84.4%) were followed up at approximately 6 months. No statistically or clinically significant effect of a MTX- or alcohol-free diet was observed on signs and symptoms of fibrocystic breast disease. On the basis of the results of the present and previous randomized controlled studies, it thus appears possible to exclude that abstention from coffee and other MTX-containing beverages can substantially reduce signs and symptoms of fibrocystic breast disease within a few month

Embryonal rhabdomyosarcoma of the orbit in a liver transplant recipient

Although an increased incidence of de novo malignancies is reported in transplant recipients, rhabdomyosarcoma, an aggressive mesenchymal tumor typical of childhood, is not considered a neoplasm commonly related to immunosuppression. A 21-year-old woman presented with unilateral diplopia and proptosis 16 months after liver transplantation for fulminant hepatic failure. A tumoral mass originating from the medial rectus muscle was partially removed and diagnosed as being an embryonal rhabdomyosarcoma. Since the patient refused complete orbital excision, one course of radiotherapy and six courses of chemotherapy were administered, while immunosuppression was re-modulated, without interruption of the administration of cyclosporine. Complete control of tumor growth was achieved, while no alterations of graft function were observed throughout the treatment period