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[Application of antisense human telomerase RNA toward cancer therapy]
1First Department of Pathology, Hiroshima University School of Medicine.
Abstract:
We overviewed recent results of anti-tumor effects and inhibition of telomerase activity in tumor cells through antisense human telomerase RNA(hTR). By introducing antisense hTR expression construct into tumor cells, reduction of telomeric DNAs and crisis or cellular senescence occurred in several human cancer cell lines. Antisense oligonucleotides to hTR synthesized with peptide nucleic acids and phosphorothioate deoxyribonucleic acids(PS) also inhibited telomerase activity in vitro. Furthermore, PS antisense hTR had significant effect to decrease tumor size and a number of metastatic nodules in a xenograft human cancer-nude mouse model. Taken together, the telomerase inhibitors targeting to hTR are expected to be novel anti-tumor agents.
Insights
Antisense targeting of human telomerase RNA (hTR) inhibits cancer cell growth and reduces tumor size. These findings suggest hTR inhibitors are promising novel anti-tumor agents.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Context:
- Telomerase is crucial for cancer cell proliferation and immortality.
- Targeting telomerase offers a potential strategy for cancer therapy.
Purpose:
- To review recent advancements in anti-tumor effects of antisense human telomerase RNA (hTR).
- To evaluate the efficacy of hTR inhibition in preclinical cancer models.
Summary:
- Introducing antisense hTR constructs into cancer cells reduced telomeric DNA, inducing crisis or senescence.
- Antisense oligonucleotides to hTR, including peptide nucleic acids and phosphorothioate deoxyribonucleic acids (PS), inhibited telomerase activity in vitro.
- PS antisense hTR significantly reduced tumor size and metastasis in a human cancer xenograft model.
Impact:
- Antisense hTR strategies demonstrate significant anti-tumor activity.
- Telomerase inhibitors targeting hTR represent a promising new class of anti-cancer therapeutics.