Inhibition of human telomerase activity by alterperylenol.
Human telomerase is a ribonucleoprotein that maintains telomeres by adding TTAGGG tandem repeat sequences using RNA template of the enzyme. Telomerase activity is highly expressed in immortalized cells but not in most somatic cells, except for some renewal tissues, such as hematopoietic stem cells. Therefore, telomerase can be a target for anticancer drugs. Here we show that a fungus metabolite, alterperylenol, inhibits human telomerase activity. Alterperylenol inhibited telomerase activity (IC50 = 30 microM), but altertoxin I, a structurally related compound, did not affect it at 1 mM. Moreover, alterperylenol did not affect the activity of viral reverse transcriptase at 1 mM.
Togashi
K
K
Antibiotics Laboratory, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kakeya
H
H
Morishita
M
M
Song
Y X
YX
Osada
H
H
D001551:Benz(a)Anthracenes / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005658:Fungi / Q000378:metabolism; D006801:Humans; D008979:Moloney murine leukemia virus / Q000201:enzymology; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors*
D001551:Benz(a)Anthracenes; D004791:Enzyme Inhibitors; D018894:Reverse Transcriptase Inhibitors; C050233:altertoxin I; D010569:Perylene; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase; C120102:alterperylenol