Inhibition of Telomerase Activity by PKC Inhibitors in Human Nasopharyngeal Cancer Cells in Culture

Abstract

Telomerase is a specialized ribonucleoprotein polymerase that adds hexanucleotides (TTAGGG) onto human chromosomal ends. The expression of telomerase activity has been associated with cell immortalization and the malignant phenotype in most cancers. How the telomerase activity is regulated in cancer cells is presently not known. In this work, the effects of cell cycle blockers, DNA damaging agents, TopII inhibitors and proteins kinase inhibitors on the telomerase activity were examined in cultured nasopharyngeal carcinoma cells NPC-076. Agents which interfere with tubulin assembly (Taxol and vinblastine) and agents which arrest cells at S phase (methotrexate and 5-fluorouracil) did not inhibit telomerase activity of treated cells. Agents which damage DNA (cisplatin, methyl methanesulfonate, and UV radiation) and TopII inhibitors (etoposide and daunorubicin) also did not inhibit telomerase activity of treated cells. Among the protein kinase inhibitors examined, no significant inhibition of telomerase activity was observed with cells treated with quercetin, H-89, or herbimycin A. On the other hand, two protein kinase C (PKC) inhibitors (bisindolylmaleimide I and H-7) were found to produce a big inhibition of telomerase activity in treated cells. Staurosporine produced a moderate inhibition, and sphingosine had a small inhibitory effect. The inhibition of telomerase activity by PKC inhibitors appears to be specific since the treated cells were mostly viable (i.e., greater than 75%) and still retained significant levels of protein synthesis capability. These results implicate that protein kinase C is involved in the regulation of telomerase activityin vivo.