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Human telomerase reverse transcriptase antisense treatment downregulates the viability of prostate cancer cells in
A Schindler1, U Fiedler, A Meye
1Department of Urology, Fetscherstrasse 74, Technical University of Dresden, Dresden, Germany.
Abstract:
Telomerase, a ribonucleoprotein complex is activated in the vast majority of human malignancies, including prostate cancer. Its inhibition is a putative way to affect cancer proliferation and might be used in the therapy of tumors. We analysed the influence of antisense phosphorothioate oligonucleotides (PTO) against the reverse transcriptase subunit of telomerase on prostate cancer cell viability, telomerase activity and telomere length. DU145 prostate cancer cells were cultivated in PTO containing medium. The PTO-incorporation was confirmed by confocal laser scanning microscopy. Cell viability was measured by a WST-1 tetrazolium assay. After 15 days of antisense PTO treatment, a significant inhibition of cell viability occurred. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay and telomere length by Southern blot analysis. Since the long-term telomerase antisense treatment reduces the viability of prostate cancer cells significantly, this antisense approach could be a new therapeutic strategy to treat patients with advanced prostate cancer.
Insights
Antisense oligonucleotides targeting telomerase significantly reduced prostate cancer cell viability and activity. This approach shows promise as a novel therapeutic strategy for advanced prostate cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Telomerase is a key enzyme activated in most human cancers, including prostate cancer.
- Telomerase inhibition is a potential therapeutic strategy for cancer treatment.
- Prostate cancer progression is linked to telomerase activity.
Purpose of the Study:
- To investigate the effect of antisense phosphorothioate oligonucleotides (PTO) targeting telomerase reverse transcriptase on prostate cancer cells.
- To evaluate the impact of this treatment on cell viability, telomerase activity, and telomere length.
Main Methods:
- DU145 prostate cancer cells were treated with antisense PTO.
- Cell viability was assessed using the WST-1 assay.
- Telomerase activity and telomere length were measured by TRAP assay and Southern blot, respectively.
- PTO incorporation was confirmed via confocal microscopy.
Main Results:
- Antisense PTO treatment led to significant inhibition of prostate cancer cell viability after 15 days.
- The treatment also reduced telomerase activity and affected telomere length.
- PTO incorporation into cells was successfully confirmed.
Conclusions:
- Long-term antisense telomerase treatment significantly reduces prostate cancer cell viability.
- This antisense approach represents a potential new therapeutic strategy for advanced prostate cancer.
- Targeting telomerase with antisense oligonucleotides is a viable option for prostate cancer therapy.