Apoptotic mechanisms of gallium nitrate: basic and clinical investigations. Oncology (Williston Park) 2004 Nov;18(13 Suppl 10):39-44
Date
01/18/2005Pubmed ID
15651176Scopus ID
2-s2.0-14144250578 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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.
Author List
Chitambar CRMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Apoptosis
Caspases
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Gallium
Humans
Hydroxyurea
In Vitro Techniques
Lymphoma
Lymphoma, Non-Hodgkin
Prognosis
Treatment Outcome
