9-Methoxy-N2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen. Neurotoxic potential of MMEA has been demonstrated in an in vitro model employing sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased staining intensity following incubation with increasing concentrations of MMEA (0.1-100 microM). Cytological evaluation of paraffin sections stained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma membrane. No glial or vascular pathology could be discerned. Autoradiography, following exposure to 14C-MMEA, revealed distinct labelling of the large neurons of the brain stem, neurons in the thalamus and pyramidal neurons of the hippocampus, indicating neuronal uptake of the drug.
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Neurotoxicology
September 1997
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
9-methoxy-N2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticine derivatives that are selectively cytotoxic to human brain tumor cell lines derived from non-neuronal (glial) cells (Acton et al, 1994). In an attempt to determine whether MMEA may exhibit toxicity to normal brain cells, we have examined the effect of the drug, in vitro, using sagittal slices of rat brain. Incubation of rat brain slices in an artificial cerebrospinal fluid medium containing MMEA resulted in dose-dependent leakage of lactate dehydrogenase (LDH) into the surrounding medium.
View Article and Find Full Text PDFNeurotoxicology
September 1997
Department of Neuropathology, National Institute of Mental Health and Neuroscience, Bangalore, India.
9-Methoxy-N2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
November 1996
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland, USA.
9-Methoxy-N2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticines that exhibited selective cytotoxicity for human brain tumor cell lines of glial origin in the in vitro primary screen of the U.S. National Cancer Institute.
View Article and Find Full Text PDFBiochem Pharmacol
January 1995
Laboratory of Drug Discovery Research and Development, Division of Cancer Treatment, Frederick, MD 21702-1201.
9-Methoxy-N2-methylellipticinium acetate (MMEA) was preferentially cytotoxic to human brain tumor cell lines in the in vitro primary screen of the U.S. National Cancer Institute.
View Article and Find Full Text PDFBiochem Biophys Res Commun
May 1994
Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, Maryland 21702-1201.
The quaternized ellipticine derivative, 9-methoxy-N2-methylellipticinium acetate (MMEA), is representative of a group of ellipticinium compounds found preferentially cytotoxic to human brain tumor cell lines comprising a subpanel of the U.S. National Cancer Institute (NCI)'s in vitro "disease-oriented" anticancer drug discovery screen.
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