Activation of polyamine catabolism by N1, N11-diethylnorspermine alters the cellular localization of mTOR and downregulates mTOR protein level in glioblastoma cells
نویسندگان
چکیده
منابع مشابه
Activation of polyamine catabolism by N1,N11-diethylnorspermine leads to cell death in glioblastoma.
Glioblastoma multiforme (GBM) is one of the most therapeutically refractory human cancers. Elevated cellular polyamine levels are a common feature of cancer cells, including GBM cells, and the polyamine pathway has been explored as a potential therapeutic target to inhibit polyamine biosynthesis or activate polyamine catabolism. In this study, we investigated the effect of N1,N11-diethyl-norspe...
متن کاملPolyamine catabolism in platinum drug action: Interactions between oxaliplatin and the polyamine analogue N1,N11-diethylnorspermine at the level of spermidine/spermine N1-acetyltransferase.
A great deal of experimental evidence connects induction of polyamine catabolism via spermidine/spermine N1-acetyltransferase (SSAT) to antiproliferative activity and apoptosis. Following our initial observation from gene expression profiling that platinum drugs induce SSAT, we undertook this present study to characterize platinum drug induction of SSAT and other polyamine catabolic enzymes and...
متن کاملTransgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N1-acetyltransferase show enhanced sensitivity to the polyamine analog, N1, N11-diethylnorspermine.
We have recently generated transgenic mice in which polyamine catabolism has been activated by overexpressing the rate-limiting enzyme of polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT). These animals have now been tested for their sensitivity to the polyamine analog N1,N11-diethylnorspermine (DENSPM), which is currently undergoing Phase I clinical trial. The analog is kno...
متن کاملCollateral sensitivity of human melanoma multidrug-resistant variants to the polyamine analogue, N1,N11-diethylnorspermine.
Certain N-alkylated analogues of the natural polyamine spermine, such as N1,N11-diethylnorspermine (DENSPM), rapidly deplete intracellular polyamine pools by down-regulating the biosynthetic enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase, and by potently up-regulating the polyamine catabolizing enzyme, spermidine/spermine N1-acetyltransferase. On the basis of previously...
متن کاملDetoxification of the polyamine analogue N1-ethyl-N11-[(cycloheptyl)methy]-4,8-diazaundecane (CHENSpm) by polyamine oxidase.
PURPOSE Analogues of the naturally occurring polyamines, alkylated on both terminal amines, are being developed as anticancer drugs. Because bisalkylated derivatives of putrescine (1,4-diaminobutane) are potent inhibitors of the flavin adenine dinucleotide-dependent polyamine oxidase (PAO), we asked whether PAO could detoxify synthetic bisalkylated polyamines with chain lengths longer than putr...
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ژورنال
عنوان ژورنال: Cancer Biology & Therapy
سال: 2007
ISSN: 1538-4047,1555-8576
DOI: 10.4161/cbt.6.10.4800