GRN163L exposure could limit the lifespan of cultivated cancer cells derived from glioblastoma, multiple myeloma and Barrett��s esophageal adenocarcinoma as well as breast, lung and liver cancers. In mouse models, the inhibitor could inhibit the growth of xenografts produced in mice by the implantation of these human cancer cells. GRN163L is currently in clinical trials in patients with multiple myeloma, essential thrombocythemia or polycythemia vera, and primary or secondary myelofibrosis. The effects of telomerase inhibition, let alone GRN163L, have never been examined in pancreatic cancer, one of the deadliest and most frequently recurring malignancies. In this report, we have tested the effects of GRN163L on a panel of 10 pancreatic cancer cell lines. With IC50 in the nanomolar range, GRN163L efficaciously inhibited telomerase in all 10 cell lines. Continuous GRN163L exposure of CAPAN1 and CD18 cells resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to the drug eventually led to crisis and to a complete loss of viability after 47 and 69 doublings, respectively. These results show that continuous exposure to GRN163L can reverse the immortal phenotype of pancreatic cancer cells. These findings should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer. Cells were plated at a density of 104 cells/well in a 24-well plate. The next day, cells were fixed and subjected to histochemical staining for human senescence-associated b-galactosidase activity. Fixation and staining was done as described previously. Without a phase contrast filter, both the MCE Company CAY10505 positively and negatively stained cells were counted under the microscope. Combining data from ten separate fields, the percent of blue cells was tabulated from a total of at least 200 counted cells. Using a non-radioactive TRAP assay, baseline telomerase activity was measured quantitatively in each cell line. The TRAP assay uses PCR to 342577-38-2 amplify the products of telomerase elongation along with an internal telomerase assay standard. Telomerase activity is quantified as the ratio of the intensity of the telomerase ladder over that of the ITAS. Figure 1C shows a representative example of a TRAP assay performed on the panel, using the sam
