Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR.
Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.
Bajpai
Arun K
AK
WelGENE Inc. 71B-4L, Hightech sector 2, Sungseo Industrial Park III, Dalseogu, Daegu 704-230, Republic of Korea.
Park
Jeong-Hoh
JH
Moon
Ik-Jae
IJ
Kang
Hyungu
H
Lee
Yun-Han
YH
Doh
Kyung-Oh
KO
Suh
Seong-Il
SI
Chang
Byeong-Churl
BC
Park
Jong-Gu
JG
D000818:Animals; D001483:Base Sequence; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008081:Liposomes; D016372:RNA, Antisense; D019098:Telomerase