Antisense telomerase induced cell growth inhibition, cell cycle arrest and telomerase activity down-regulation in gastric and colon cancer cells.
BACKGROUND
Antisense telomerase RNA (anti-hTR) coupled with 2',5'-linked tetraadenylate (2-5A) shows an inhibitory effect on cell growth and induces apoptosis in certain kinds of cancer. This experiment examined the anti-hTR effect on gastric and colorectal cancer cells.


METHODS
Gastric cancer cells CRL-5822, CRL-5971 and colorectal cancer cells HTB-38, CCL-247 were treated with repeated doses of anti-hTR. Cell growth and cell cycle parameters were analysed. Telomerase activity was measured by TRAP assay. Control oligonucleotides and normal fibroblast were used as control.


RESULTS
After two doses of anti-hTR, the cell viability for CRL-5822, CRL-5971, HTB-38 and CCL-247 cells was reduced to 15%, 12%, 37% and 37%, respectively. The DNA histogram showed cells arrested at the G2/M-phase and the sub-G1 peak found indicated that apoptosis had occurred.


CONCLUSIONS
Anti-hTR demonstrated inhibition of cell growth and cell cycle arrest on gastric and colorectal cancer cells through a telomerase regulation pathway. Its specificity towards cancerous tissues but not normal tissues suggested a potential for anti-cancer therapy.
Wong
Stephen C H
SC
National University Medical Institute, Faculty of Medicine, National University of Singapore, Singapore.
Yu
Hanry
H
Moochhala
Shabbir M
SM
So
Jimmy B Y
JB
D000227:Adenine Nucleotides / Q000235:genetics / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009843:Oligoribonucleotides / Q000235:genetics / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D016372:RNA, Antisense; C023505:2',5'-oligoadenylate; D019098:Telomerase