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Noscapine crosses the blood-brain barrier and inhibits
glioblastoma growth
Landen JW, Hau V, Wang M, Davis T, Ciliax B, Wainer BH, Van Meir EG, Glass
JD, Joshi HC, Archer DR
Department of Cell Biology, Emory University School of Medicine, Atlanta,
Georgia 30322, USA.
The opium alkaloid noscapine is a commonly used antitussive agent available in
Europe, Asia, and South America.
Although the mechanism by which it suppresses
coughing is currently unknown, it is presumed to involve the central nervous
system.
In addition to its antitussive action, noscapine also binds to tubulin
and alters microtubule dynamics in vitro and in vivo.
In this study, we show
that noscapine inhibits the proliferation of rat C6 glioma cells in vitro
(IC(50) = 100 microm) and effectively crosses the blood-brain barrier at rates
similar to the ones found for agents such as morphine and [Met]enkephalin that
have potent central nervous system activity (P < or = 0.05).
Daily oral
noscapine treatment (300 mg/kg) administered to immunodeficient mice having
stereotactically implanted rat C6 glioblasoma into the striatum revealed a
significant reduction of tumor volume (P < or = 0.05).
This was achieved with
no identifiable toxicity to the duodenum, spleen, liver, or hematopoietic cells
as determined by pathological microscopic examination of these tissues and flow
cytometry.
Furthermore, noscapine treatment resulted in little evidence of
toxicity to dorsal root ganglia cultures as measured by inhibition of neurite
outgrowth and yielded no evidence of peripheral neuropathy in animals.
However,
evidence of vasodilation was observed in noscapine-treated brain tissue.
These
unique properties of noscapine, including its ability to cross the blood-brain
barrier, interfere with microtubule dynamics, arrest tumor cell division, reduce
tumor growth, and minimally affect other dividing tissues and peripheral nerves,
warrant additional investigation of its therapeutic potential.
PMID: 15297423 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15297423
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