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2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells

Cancer Gene Therapy volume 9, pages 624–630 (2002)Cite this article

Abstract

Human telomerase RNA (hTR), an important component of telomerase, is a possible target of telomerase-based cancer gene therapy. The present study was undertaken to assess the efficacy of antisense hTR therapy using newly developed 2-5A (5′-phosphorylated 2′-5′–linked oligoadenylate)–linked oligonucleotides against cervical cancer cells. ME180 and SiHa cells were treated with 2-5A–linked antisense hTR designed to complement the region of hTR between residues 76 and 94. The hTR expression, telomerase activity, cell viability, and apoptosis were then examined. The 2-5A anti-hTR effectively degraded hTR and inhibited telomerase activity. The 2-5A mutant anti-hTR and the anti-hTR without 2-5A were not capable of inhibiting telomerase activity. Inhibition of telomerase by 2-5A anti-hTR rapidly decreased cell viability only in telomerase-positive cells within 3–6 days after the treatment, when telomere length has not yet been shortened. This inhibition was associated with apoptosis, possibly through activation of caspase family members. These findings suggest that 2-5A–linked antisense-hTR therapy has a potent telomerase-inhibitory effect associated with a cytocidal effect from caspase-induced apoptosis, and may therefore be a potential tool in telomerase-based gene therapy against cervical cancers.

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Acknowledgements

This study was supported in part by a grant-in-aid for the Second-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, 13-1, Takaramachi, Kanazawa, 920-8641, Ishikawa, Japan

    Noriyuki Yatabe, Satoru Kyo, Taro Kanaya, Zhuo Wang, Yoshiko Maida, Masahiro Takakura, Mitsuhiro Nakamura, Masaaki Tanaka & Masaki Inoue

  2. Department of Neurosurgery, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York, 10029-6574, USA

    Seiji Kondo

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  1. Noriyuki Yatabe
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Correspondence to Satoru Kyo.

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Yatabe, N., Kyo, S., Kondo, S. et al. 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells. Cancer Gene Ther 9, 624–630 (2002). https://doi.org/10.1038/sj.cgt.7700479

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