RRC ID 43206
Author Mikami-Terao Y, Akiyama M, Yuza Y, Yanagisawa T, Yamada O, Yamada H.
Title Antitumor activity of G-quadruplex-interactive agent TMPyP4 in K562 leukemic cells.
Journal Cancer Lett.
Abstract 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 microM TMPyP4 significantly inhibited the growth of both types of cell, with decreases of cells in the G(1) phase and increases of those in the S and G(2)/M phases after 48 h, 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 microM TMPyP4 for 48 h. 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.
Volume 261(2)
Pages 226-34
Published 2008-3-18
DOI 10.1016/j.canlet.2007.11.017
PII S0304-3835(07)00571-X
PMID 18096315
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Blotting, Southern Blotting, Western Cell Cycle / drug effects DNA Primers / chemistry Enzyme Inhibitors / pharmacology* G-Quadruplexes / drug effects* Gene Expression Profiling Humans K562 Cells / drug effects Oligonucleotide Array Sequence Analysis Porphyrins / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Telomerase / antagonists & inhibitors* Telomere / physiology*
IF 6.491
Times Cited 52
Human and Animal Cells