Abstract
BACKGROUND: Limited treatment options and an aggressive nature make glioblastoma multiforme (GBM) a highly deadly cancer associated with poor prognosis and short survival. Gallium (Ga), an iron-mimetic metal, disrupts tumor iron homeostasis, thus effecting potential antineoplastic activity. Here we present compelling evidence that gallium maltolate (GaM) has a profound antitumor effect on GBM in vitro and in vivo. METHODS: The in vitro cytotoxic effects of GaM were measured by MTT assay in human U87 and D54 GBM cells, and cells isolated from normal rat brain. The in vivo antineoplastic effect of GaM was studied in a xenograft model that involved stereotactic inoculation of U87 cells into the right hemisphere of 8-week old male athymic rats. Following tumor growth confirmation on Day 8 post-inoculation by magnetic resonance imaging (MRI), rats received continuous intravenous (IV) administration of GaM (50 µM) for 10 days. Follow-up MRI occurred on Day 18 post-inoculation. RESULTS: In vitro, GaM profoundly inhibited the proliferation of both U87 and D54 GBM cell lines, but not control cells. The IC50 decreased 46% from 79.8 µM (3-day incubation) to 42.8 µM (5-day incubation) in U87 cells, and 24% from 51.4 µM (3 days) to 38.9 µM (5 days) in D54 cells. Removing GaM on days 3 and 5, and maintaining cells for another 5 days, caused a further decrease in IC50 (U87: 47.4% and 21.8%, respectively; D54: 11.8% and 10.3%, respectively). In vivo, rats receiving IV GaM tolerated the drug well, and no adverse effects were observed. Contrast-agent enhancing tumor volume on T1-weighted MRI increased in both treated (n = 8) and untreated (n = 7) animals, but significantly less so in treated rats. Mean percent increase in cerebral blood volume, determined from steady-state post-MION images, was 45% (controls) and 28% (treated rats) (p < 0.05). CONCLUSION: Gallium maltolate shows great promise for therapeutic potential in GBM.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
