<i>In vitro </i>and <i>in vivo </i>inhibition of telomerase activity from Chinese hamster V79 cells

Abstract

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)₄inhibited telomerase activity <i>in</i> <i>vitro. </i>In the present stud y,

we report inhibition of lelomerase 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<span style="mso-bidi-font-style:italic">μ<i style="mso-bidi-font-style: normal">M</i> of 7-deaza dATP and 0.1<span style="font-size:12.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" hiddenhorzocr;mso-bidi-font-style:italic"="">μ<i style="mso-bidi-font-style: normal">M</i> of PS-TT AGGG being the concentration for 50% of the maximum inhibition. This observation support s our earlier hypothesis that incorporation of a modified nucleotide into telomere possibly interferes with the recognition of the telomerase and TT AGGG 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.

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