In vitro and in vivo inhibition of telomerase activity from Chinese hamster V79 cells.
While studying the inhibition of telomerase activity in Chinese hamster V79 cells using polymerase chain reaction (PCR) based telomeric repeat amplification protocol (TRAP) assay, we had earlier observed that 7-deaza deoxy guanosine triphosphate (7-deaza dGTP) and oligonucleotide (TTAGGG)4 inhibited telomerase activity in vitro. In the present study, we report inhibition of telomerase activity by modified base 7-deaza deoxy adenosine triphosphate (7-deaza dATP) and phosphorothioate TTAGGG (PS-TTAGGG). Both the compounds inhibited telomerase activity in a concentration dependent manner; 8.5 microM of 7-deaza dATP and 0.1 microM of PS-TTAGGG being the concentration for 50% of the maximum inhibition. This observation supports our earlier hypothesis that incorporation of a modified nucleotide into telomere possibly interferes with the recognition of the telomerase and TTAGGG interferes with the RNA component of telomerase. We have further shown that treatment of cells with nicotinamide (NA) and benzamide (BA), well known inhibitors of poly (ADP-ribose) polymerase, reduced telomerase activity. We speculate that modification of the telomeric binding proteins or other components by poly (ADP-ribosyl)ation may be involved in such inhibition.
Pandit
B
B
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Calcutta 700 064, India.
Bhattacharyya
N P
NP
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003720:Densitometry; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009536:Niacinamide / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
D001549:Benzamides; D003848:Deoxyguanine Nucleotides; C065361:2'-deoxy-7-deazaguanosine triphosphate; D009536:Niacinamide; C037689:benzamide; D019098:Telomerase