daw
05-18-2004, 06:23 PM
Telomerase Inhibitor Arrests Growth of Barrett's-Associated Adenocarcinoma Cells
NEW YORK (Reuters Health) May 11 - PPA, a selective telomerase inhibitor, arrests the growth of Barrett's esophagus adenocarcinoma (BEAC) cells in vitro, according to a report in the May issue of Gastroenterology.
Telomerase activity is increased in Barrett's esophagus mucosa and even higher in Barrett's-associated adenocarcinoma, the authors explain, suggesting that telomerase inhibitors might prove beneficial as chemoprevention or anticancer therapy in affected individuals.
Dr. Nikhil C. Munshi from Dana Farber Cancer Institute, Boston and colleagues investigated the effects of PPA on telomerase activity, telomere length, growth, and apoptosis in two BEAC cell lines.
Telomerase inhibitor PPA at 10 micromoles/L for 5 to 7 days brought nearly complete inhibition of telomerase activity in both BEAC cell lines, the authors report, and a marked arrest of cell proliferation followed. By day 21, viable cell numbers had declined by 75% to 99%.
BEAC colony sizes were unaffected by 1 week of treatment, the report indicates, but 3 weeks of treatment with PPA was associated with a marked reduction in number and size of colonies. Colony size and number of normal intestinal cells, however, were unaffected by exposure to PPA.
PPA treatment was associated with marked reductions in telomere length in BEAC cells, the researchers note, and treatment resulted in induction of apoptosis in the majority of cells of both BEAC cell lines.
These changes occurred in the absence of significant changes in gene expression following PPA treatment, the investigators report.
"These studies provide a strong rationale for the potential use of telomerase inhibitors in chemoprevention and treatment of Barrett's-associated adenocarcinoma," the authors conclude.
Gastroenterology 2004;126:1337-1346.
NEW YORK (Reuters Health) May 11 - PPA, a selective telomerase inhibitor, arrests the growth of Barrett's esophagus adenocarcinoma (BEAC) cells in vitro, according to a report in the May issue of Gastroenterology.
Telomerase activity is increased in Barrett's esophagus mucosa and even higher in Barrett's-associated adenocarcinoma, the authors explain, suggesting that telomerase inhibitors might prove beneficial as chemoprevention or anticancer therapy in affected individuals.
Dr. Nikhil C. Munshi from Dana Farber Cancer Institute, Boston and colleagues investigated the effects of PPA on telomerase activity, telomere length, growth, and apoptosis in two BEAC cell lines.
Telomerase inhibitor PPA at 10 micromoles/L for 5 to 7 days brought nearly complete inhibition of telomerase activity in both BEAC cell lines, the authors report, and a marked arrest of cell proliferation followed. By day 21, viable cell numbers had declined by 75% to 99%.
BEAC colony sizes were unaffected by 1 week of treatment, the report indicates, but 3 weeks of treatment with PPA was associated with a marked reduction in number and size of colonies. Colony size and number of normal intestinal cells, however, were unaffected by exposure to PPA.
PPA treatment was associated with marked reductions in telomere length in BEAC cells, the researchers note, and treatment resulted in induction of apoptosis in the majority of cells of both BEAC cell lines.
These changes occurred in the absence of significant changes in gene expression following PPA treatment, the investigators report.
"These studies provide a strong rationale for the potential use of telomerase inhibitors in chemoprevention and treatment of Barrett's-associated adenocarcinoma," the authors conclude.
Gastroenterology 2004;126:1337-1346.