Antitumor activity of G-quadruplex–interactive agent TMPyP4 in K562 leukemic cells

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 μM TMPyP4 significantly inhibited the growth of both types of cell, with decreases of cells in the G1 phase and increases of those in the S and G2/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 μM TMPyP4 for 48 h. Moreover, TMPyP4 decreased c-Myc protein expression, increased the expression of p21CIP1 and p57KIP2 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.