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In vitro and in vivo effect of human lactoferrin on glioblastoma growth

Antonietta Arcella, Maria Antonietta Oliva, Sabrina Staffieri, Silvia Aalberti, Giovanni Grillea, Michele Madonna, Marcello Bartolo, Luigi Pavone, Felice Giangaspero, Giampaolo Cantore, and Alessandro Frati

OBJECT

Human lactoferrin (HLF) is a natural protein with antitumor activity. The aim of this study was to investigate the effects of HLF alone and in combination with temozolomide (TMZ), a conventional chemotherapeutic, on human glioblastoma (GBM) cells.

METHODS

The authors cultured fresh human primary cell lines NMD and FN and the continuous cell line U87MG to evaluate proliferation in the presence of HLF alone at different doses (1, 10, and 100 mg/ml, and 1 mg/ml) and in combination with TMZ. In in vivo experiments they assessed tumor size reduction in CD1 nude mice carrying an orthotopic GBM xenograft and orally treated with HLF.

RESULTS

Lactoferrin causes growth inhibition in the NMD and FN primary cell lines and in the U87MG continuous cell line. This inhibition seemed to be modulated by the downregulation of cyclin D1 and D4. Western blot and fluorescence-activated cell sorting analysis showed inhibition of the cell cycle in G0/G1 and G2 phases. When administered in nude mice, HLF (60 mg/kg/day) decreased tumor size about 30%, as shown in both histological analyses and high-field brain MRI. Administration of HLF with TMZ enhanced the effect of chemotherapy both in vitro and in vivo.

CONCLUSIONS

This study demonstrated that HLF can inhibit GBM cell growth, suggesting that this nontoxic substance may have a role in potentiating the effect of current TMZ treatment of GBM.