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Treatment of prostate cancer in vitro and in vivo with 2-5A-anti-telomerase RNA component

Oncogene volume 19, pages 2205–2211 (2000)Cite this article

Abstract

Prostate cancer is the most common malignancy of elderly men in the United States. Since there is no curative treatment for advanced prostate cancer, exploration of novel modalities of treatment is essential. Telomerase, a ribonucleoprotein, is detected in the vast majority of prostate cancer, but not in normal or benign prostatic hyperplasia tissues. Thus, telomerase is expected to be a very strong candidate for targeted therapy of prostate cancer. In this study, we synthesized a 19-mer antisense oligonucleotide against the RNA component of human telomerase (hTR) linked to a 2-5A molecule (2-5A-anti-hTR) and examined its cytotoxic effect on prostate cancer cells. The 2-5A antisense strategy relies on the recruitment and activation of RNase L at the site of targeted RNA sequence. We here show that treatment with 2-5A-anti-hTR in the presence of a cationic liposome reduced cell viability of tumor cell lines tested to 9–18% within 6 days. In contrast, normal fibroblast cells were resistant to the treatment. Its effect was mainly due to induction of apoptosis by activated caspase family members. Furthermore, treatment of subcutaneous tumors in nude mice with 2-5A-anti-hTR significantly suppressed the tumor growth through induction of apoptosis (P<0.001). The treatment with 2-5A-anti-hTR may be a promising strategy for the treatment modality of prostate cancer with telomerase activity.

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Acknowledgements

We thank Dr Robert H Silverman for a critical review and Dr John K Cowell for 2-5A-anti-hTR. This study was supported in part by John Gagliarducci Fund (S Kondo.), Cleveland Clinic Foundation Research Fund #5928 (S Kondo), and the United States Public Health Service Grant (1R01CA80233) (S Kondo) awarded by National Cancer Institute.

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Authors and Affiliations

  1. The Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, 44195, Ohio, OH, USA

    Yasuko Kondo, Shoji Koga, Tadashi Komata & Seiji Kondo

  2. Department of Neurosurgery, The Cleveland Clinic Foundation, Cleveland, 44195, Ohio, OH, USA

    Seiji Kondo

  3. Department of Neurosurgery, The Mount Sinai Medical Center, New York, 10029, NY, USA

    Yasuko Kondo, Tadashi Komata & Seiji Kondo

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  1. Yasuko Kondo
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Kondo, Y., Koga, S., Komata, T. et al. Treatment of prostate cancer in vitro and in vivo with 2-5A-anti-telomerase RNA component. Oncogene 19, 2205–2211 (2000). https://doi.org/10.1038/sj.onc.1203538

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