hTERT/re-caspase-3 system induce apoptosis in hTERT-positive cancer cells.
Apoptosis induction is a promising approach for the treatment of human cancer. To achieve this purpose, the design of an expression system capable to induce apoptosis specifically in cancer cells is essential. Telomerase is an attractive target for delivery of apoptotic genes as an overwhelming majority of cancers have telomerase activity whereas most normal cells have low or an absence of telomerase activity. Activation of telomerase is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). In the present study, we developed a telomerase-specific delivery system of apoptosis-inducible gene re-Caspase-3, through utilizing the promoter of the hTERT gene, and then investigated its antitumor effect on cancer cells and tissues. The reason we used the re-Caspase-3 gene is that it is capable of autocatalytic processing and inducing apoptosis independent of the initiator Caspases. Here, we demonstrated that the hTERT/re-Caspase-3 system induced apoptosis in hTERT-positive cancer cells: CNE1 (nasopharyngeal carcinoma), HRT-18 (colonic carcinoma), MGC (stomath carcinoma), but not in hTERT-low Hacat (human normal keratinize epithelium) cells. In addition, the growth of s.c. tumors in nude mice was suppressed significantly by the treatment with the hTERT/re-Caspase-3 system. Results suggested that the telomerase-specific transfer of there-Caspase-3 gene may be an effective and promising targeting approach for the treatment of cancer.
Yang
Li-fang
LF
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.
Zhao
Yan
Y
Zeng
Liang
L
Gong
Jian-ping
JP
Cao
Ya
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D017931:DNA Primers; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D014183:Transplantation, Heterologous
D017931:DNA Primers; D012333:RNA, Messenger; D019098:Telomerase; D053148:Caspase 3