Clinical studies have shown gallium nitrate to have significant antitumor activity against non-Hodgkin's lymphoma and bladder cancer, thus indicating that gallium-based drugs have potential for further development as antineoplastic agents. In this study, we compared the cytotoxicity of gallium maltolate, a novel gallium compound, with gallium nitrate in lymphoma cell lines, including p53 variant and unique gallium nitrate-resistant cells. We found that gallium maltolate inhibited cell proliferation and induced apoptosis through the mitochondrial pathway at lower concentrations and more rapidly than gallium nitrate. Gallium maltolate produced an increase in intracellular reactive oxygen species (ROS) within 2 h of incubation with cells; this effect could be blocked by mitoquinone, a mitochondria-targeted antioxidant. The role of the transferrin receptor (TfR) in gallium maltolate's action was examined using monoclonal antibody (MoAb) 42/6 to block TfR function. However, although MoAb 42/6 reduced gallium maltolate-induced caspase-3 activity, it had only a minor effect on cell growth inhibition. Importantly, gallium maltolate induced apoptosis in cells resistant to gallium nitrate, and, unlike gallium nitrate, its cytotoxicity was not affected by cellular p53 status. Cellular gallium uptake was greater with gallium maltolate than with gallium nitrate. We conclude that gallium maltolate inhibits cell proliferation and induces apoptosis more efficiently than gallium nitrate. Gallium maltolate is incorporated into lymphoma cells to a greater extent than gallium nitrate via both TfR-independent and -dependent pathways; it has significant activity against gallium nitrate-resistant cells and acts independently of p53. Further studies to evaluate its antineoplastic activity in vivo are warranted.
[Show abstract][Hide abstract] ABSTRACT: Metal-based coordination compounds have been used throughout the history of human medicine to treat various diseases, including cancer. Since the discovery of cisplatin in 1965, a great number of metal coordination complexes, such as platinum, ruthenium, gold or copper have been designed, synthesized and tested in order to develop clinically effective and safe drugs. Currently, many reviews cover applications of cytostatic metal complexes pointing out the most promising examples of platinum- and non-platinum-based compounds in preclinical and clinical trials. However, recent comprehensive reviews covering chemical and biological aspects of metal-based coordination compounds in cancer therapy are still rare. In this review we wish to provide an overview of the coordination chemistry of current and novel cytostatic compounds, including an outline of their design and rationale of synthesis, and summarize bio-chemical reactivity and physicochemical properties of candidate metal complexes.
"At that time, it was hypothesized that there was a close correlation between gallium-67 uptake and degree of malignancy of thyroid tumor cells, even if the mechanism of tumor localization of gallium-67 was still unclear [92, 93]. Nowadays it is commonly accepted that gallium-67 citrate is preferentially uptaken by high-grade malignant tumors, through its ability to bind, in place of transferrin, TfR1/CD71 [94–96]. This is supported by the evidence that only malignant tumors that overexpressed TfR1/CD71 at a tissue level were also marked in vivo by gallium [97–99]. "
[Show abstract][Hide abstract] ABSTRACT: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers. Actually, ATC is refractory to conventional therapies, including surgery, chemotherapy, radiotherapy, and radioiodine ((131)I) therapy. Accordingly, genetic and molecular characterizations of ATC have been frequently and periodically reviewed in order to identify potential biological markers exploitable for target therapy. This review briefly focuses on main molecular events that characterize ATC and provides an update about preclinical studies. In addition, the overexpression of transferrin receptor 1 (TfR1/CD71) by neoplastic cells of ATC is emphasized in that it could represent a potential therapeutic target. In this regard, new therapeutic approaches based on the use of monoclonal or recombinant antibodies, or transferrin-gallium-TfR1/CD71 molecular complexes, or lastly small interfering RNAs (siRNAs) are proposed.
International Journal of Endocrinology 07/2014; 2014:685396. DOI:10.1155/2014/685396 · 1.95 Impact Factor
") ligands in a stable coordination chemistry, with increased solubility and reduced likelihood of forming toxic precipitates. Preclinical studies of the cytotoxicity on various cell lines in vitro have shown that GaM is more efficient than Ga(NO 3 ) 3 in inhibiting cell growth, likely depending on a more efficient entrance of the compound into the cells . Moreover, GaM showed improved absorption and bioavailability compared with other orally administrated Ga(III) salts  "
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