N-butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

Abnormalities in glycosphingolipid (GSL) biosynthesis have been implicated in the oncogenesis and malignancy of brain tumours. GSLs comprise the gangl iosides and the neutral GSLs and are major components of the cell surface g lycocalyx. N-butyldeoxynojirimycin (NB-DNJ) is an imino sugar that inhibits the glucosyltransferase catalysing the first step in GSL biosynthesis. The influence of NB-DNJ was studied on the growth and ganglioside composition of two 20-methylcholanthrene-induced experimental mouse brain tumours, EPEN and CT-2A, which were grown in vitro and in vivo. NB-DNJ (200 muM) inhibit ed the proliferation of the EPEN and CT-2A cells by 50%, but did not reduce cell viability. The drug, administered in the diet (2400 mg kg(-1)) to adu lt syngeneic C57BL/6 mice, reduced the growth and ganglioside content of su bcutaneous and intracerebral EPEN and CT-2A tumours by at least 50% compare d to the untreated controls. NB-DNJ treatment also shifted the relative dis tribution of tumour gangliosides in accordance with the depletion of metabo lic substrates. Side effects of NB-DNJ treatment were generally mild and in cluded reductions in body and spleen weights and intestinal distension. We conclude that NB-DNJ may inhibit tumour growth through an effect on ganglio side biosynthesis and may be useful as a new chemotherapy for brain tumours . (C) 2001 Cancer Research Campaign.