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

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 ri bsnucleoprotein, is detected in the vast majority of prostate cancer, but n ot in normal or benign prostatic hyperplasin tissues. Thus, telomerase is e xpected to be a very strong candidate for targeted therapy of prostate canc er. In this study, we synthesized a 19-mer antisense oligonucleotide agains t 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. Th e 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 turner cell lines tested to 9-18% within 6 days, In contrast, normal fib roblast cells mere resistant to the treatment. Its effect was mainly due to induction of apoptosis by activated caspase family members. Furthermore, t reatment of subcutaneous tumors in nude mice with 2-SA-anti-hTR significant ly 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 treatm ent modality of prostate cancer with telomerase activity.