K252a inhibits proliferation of glioma cells by blocking platelet-derived growth
factor signal transduction.
Chin LS, Murray SF, Zitnay KM, Rami B.
Department of Neurosurgery, Program in Oncology, University of Maryland School
of Medicine, Baltimore, Maryland 21201, USA. lchin@surgery1.ab.umd.edu
Growth factors are known to regulate glioma proliferation. The glioma cell lines
U87 and T98G were examined for evidence of an autocrine stimulatory loop
involving the neurotrophin family of growth factors. Although neurotrophin-3 and
TrkC RNA were detected by reverse transcription-PCR, there was no evidence of
significant interaction between neurotrophin-3 and its cognate receptor TrkC.
The microbial alkaloid K252a has been described to inhibit both Trk tyrosine
kinase activity and neuroblastoma cell proliferation. K252a inhibited
proliferation in U87 (IC50 = 1170 nM) and T98G (IC50 = 529 nM) but induced
apoptosis in U87 cells only. At concentrations of 500 nM to 1 microM, K252a
blocked only platelet-derived growth factor (PDGF)-mediated receptor
autophosphorylation. These results suggest that an autocrine loop involving PDGF
is functional and important for maintaining tumor growth. There is no evidence
to support the existence of a neurotrophin-mediated autocrine loop. K252a,
through inhibition of PDGF signal transduction, may be a novel therapeutic agent
in the treatment of human gliomas.
Publication Types:
Research Support, Non-U.S. Gov't
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