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Cytotoxicity of L-cycloserine against human neuroblastoma and medulloblastoma cells is associated with the suppression of ganglioside expression.

Abstract：

BACKGROUND:Human neuroblastoma and medulloblastoma express abnormal ganglioside patterns especially GD2 and GM2 which are important for tumour growth. We tested the effects of L-cycloserine (L-CS), a potent inhibitor of synthesis of glycosphingolipids, on the growth, viability and expression of GD2 and GM2 in neuroblastoma and medulloblastoma cells. MATERIALS AND METHODS:The cytotoxic effects of L-CS were tested using the MTT dye reduction assay on four neuroblastoma (IMR-32, SK-N-SH, UKF-NB-2 and UKF-NB-3), two medulloblastoma (D283 and D341) and normal human fibroblasts and epithelial cell lines. In some experiments cytotoxicity of L-CS was tested in the presence of exogenous GD2 and GM2. The expression of GD2 and GM2 was analysed by flow cytometry. The antitumoral effects of L-CS in vivo were assessed on established xenografts of UKF-NB-3 or D283 cells in athymic (nude) mice using systemic administration of the drug (150 mg/kg intraperitoneally, once per day on 20 consecutive days). RESULTS:In vitro experiments revealed that L-CS was toxic for tumour cells at concentrations ranging from 0.5 to 20 micrograms/ml without any significant effects on normal fibroblasts and epithelial cells. L-CS treatment of UKF-NB-3 and D283 cells significantly inhibited expression of GD2 and GM2. The addition of exogenous GD2 and GM2 to culture medium partially prevented cytotoxic effects of L-CS on tumour cells. In vivo treatment resulted in complete tumour regression of UKF-NB-3 xenografts whereas growth of D283 xenografts was reduced by 60%. CONCLUSIONS:L-CS is a selective antitumoral agent for neuroblastoma and medulloblastoma cells with the ability to reduce expression of tumour associated gangliosides. In vivo experiments suggest that L-CS may be effective drug for treatment of neuroblastoma and medulloblastoma.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Cinatl J Jr,Cinatl J,Kotchetkov R,Pouckova P,Vogel JU,Rabenau H,Michaelis M,Kornhuber B

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

5349-54

issue

eissn

0250-7005

issn

1791-7530

journal_volume

pub_type

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Cytotoxicity of L-cycloserine against human neuroblastoma and medulloblastoma cells is associated with the suppression of ganglioside expression.