Antibiotic G-418 is a new aminoglycoside produced by a new species of Micromonospora, M. rhodorangea NRRL 5326, with a similar structure to gentamicin B1 and has broad-spectrum antibacterial activity in vitro and in vivo, such as protozoa, amoebae, tapeworm, and pinworm infections in mice, and blocks polypeptide synthesis by inhibiting the elongation step in both prokaryotic and eukaryotic cells[3]. G418 was found to kill Acanthamoeba trophozoites with IC50 and IC90 values of 32 ± 3 and 75 ± 5 μg/mL at 37 °C respectively and induced programmed cell death through the elevation of intracellular calcium and cytochrome c translocation[4]. G418 at 1000 µg/ml was shown to have considerable influence on the growth and metabolism of CHO 679 and BHK 570 cell lines, which was correlated with the copy number and expression of the resistance protein neomycin[5]. It was also found that G418 is an allosteric activator of phosphatidylinositol-specific phospholipase C (PI-PLC) in Bacillus cereus[6].
体内研究
To investigate the treatment of proximal spinal muscular atrophy (SMA), G-418 disulfate (14 mg/kg in saline) was administered intraperitoneally to dSMA mice once a day for twelve days. G-418 disulfate treatment of SMA mice increased SMN proteins and mouse locomotion function[10].
体外研究
Hamster kidney fibroblasts BHK-21, human cervical cancer cells HeLa, mouse embryonic cells 3T3 and hamster ovary cells CHO-K1 were treated with G-418 disulfate (0-10,000 µg/mL) for 24 h. Cell growth inhibition was examined by MTT. G-418 disulfate dose-dependently inhibited the BHK-21, G-418 disulfate dose-dependently inhibited the growth of BHK-21, HeLa, 3T3 and CHO-K1 cells with IC50 of 69/483/213/311 µg/mL, respectively[7]. Human immortalised osteoblasts, hFOB 1.19, were cultured in DMEM/F12 medium containing G-418 disulfate (0.3 mg/mL). G-418 disulfate maintained the resistance of hFOB 1.19 cells to NEO[8]. Plasmid-transfected human lung adenocarcinoma cells A549 were screened with G-418 disulfate (800 μg/ml) and occasionally treated with a maintenance dose of G-418 disulfate (400 μg/mL).G-418 disulfate screens and maintains cells with NEO resistance[9].
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