Apoptotic mechanisms of gallium nitrate: basic and clinical investigations.

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Chitambar CR

Apoptotic mechanisms of gallium nitrate: basic and clinical investigations.

Oncology (Williston Park). 2004 Nov;18(13 Suppl 10):39-44.

PubMed ID

15651176 [ View in PubMed

]

Abstract

Gallium nitrate inhibits the growth of various lymphoma cell lines in vitro and exhibits antitumor activity in patients with lymphoma. The mechanism(s) of cytotoxicity is (are) only partly understood but appears to involve a two-step process: (1) targeting of gallium to cells, and (2) acting on multiple, specific intracellular processes. Gallium shares certain chemical properties with iron; therefore, it binds avidly to the iron transport protein transferrin. Transferrin-gallium complexes preferentially target cells that express transferrin receptors on their surface. Expression of transferrin receptors is particularly high on lymphoma cells. Cellular uptake of the gallium-transferrin complex leads to inhibition of cellular proliferation primarily via disruption of iron transport and homeostasis and blockade of ribonucleotide reductase. Recent studies have shown that cellular uptake of gallium leads to activation of caspases and induction of apoptosis. In phase II trials in patients with relapsed or refractory lymphoma, the antitumor activity of gallium nitrate is similar to, or better than, that of other commonly used chemotherapeutic agents. Gallium nitrate is not myelosuppressive and may be used in patients with neutropenia or thrombocytopenia. A multicenter trial to evaluate the use of gallium nitrate in patients with relapsed non-Hodgkin's lymphoma is currently ongoing.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Gallium nitrate	Ribonucleoside-diphosphate reductase subunit M2	Protein	Humans	Unknown	Inhibitor	Details

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Gallium nitrate	Serotransferrin	Protein	Humans	Unknown	Binder	Details