Journal
CANCER LETTERS
Volume 261, Issue 2, Pages 226-234Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2007.11.017
Keywords
cationic porphyrin; G-quadruplex; telomere; telomerase; mitogen-activated protein kinases
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The cationic porphyrin TMPyP4 can bind to and stabilize DNA guanine-quadruplexes. We investigated the molecular mechanism of the antitumor activity of TMPyP4 in K562 cells and human telomere reverse transcriptase subunit (hTERT)-transfected K562 cells in which telomerase activity, followed by telomere elongation, was enhanced. Treatment with 100 mu M TMPyP4 significantly inhibited the growth of both types of cell, with decreases of cells in the G, phase and increases of those in the S and G(2)/M phases after 48 It, preceding cell death after 72 h. cDNA microarray analysis revealed upregulation of 33 genes and downregulation of 54 genes in K562 cells treated with 100 mu M TMPyP4 for 48 It. Moreover.. TMPyP4 decreased c-Myc protein expression, increased the expression of p21(CIp1) and p57(KIP2) proteins, and activated p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular signal- regulated kinase. These findings may provide a rationale for the development of guanine-quadruplex-interactive agents as novel antileukemic therapies. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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