Synthetic nucleosides and nucleotides. 43. Inhibition of vertebrate telomerases by carbocyclic oxetanocin g (C.OXT-G) triphosphate analogues and influence of C.OXT-G treatment on telomere length in human HL60 cells.
Telomerase, responsible for telomere synthesis, is expressed in approximately 90% of human tumor cells but seldom in normal somatic cells. In this study, inhibition by carbocyclic oxetanocin G triphosphate (C. OXT-GTP) and its analogues was investigated in order to clarify the susceptibility of telomerase to various nucleotide analogues. C. OXT-GTP competitively inhibited telomerase activity with respect to dGTP However, C. OXT-GTP had a potent inhibitory effect on DNA polymerase alpha. It was examined whether the nucleoside (C. OXT-G) was able to alter telomere length in cultured human HL60 cells. Contrary to expectation, long-term treatment with 10 microM C. OXT-G was found to cause telomere lengthening.
Yamaguchi
Toyofumi
T
Department of Biosciences and Biotechnology Research Center, Teikyo University of Science and Technology, Uenohara, Yamanashi, Japan. toyofumi@ntu.ac.jp
Saneyoshi
Mineo
M
Takahashi
Hazuki
H
Hirokawa
Sachiko
S
Amano
Rie
R
Liu
Xiaohong
X
Inomata
Motoko
M
Maruyama
Tokumi
T
D000818:Animals; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D012474:Salmon / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
C057479:oxetanocin G; D006147:Guanine; D006160:Guanosine Triphosphate; D019098:Telomerase