Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Bernal Buenos Aires, Argentina.
Front Oncol. 2012 Sep 6;2:113. doi: 10.3389/fonc.2012.00113. eCollection 2012.
Telomerase is a highly specialized reverse transcriptase (RT) and the maintenance of telomeric length is determined by this specific enzyme. The human holoenzyme telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA component, hTR, and a group of associated proteins. Telomerase is normally expressed in embryonic cells and is repressed during adulthood. The enzyme is reexpressed in around 85% of solid tumors. This observation makes it a potential target for developing drugs that could be developed for therapeutic purposes. The identification of the hTERT as a functional catalytic RT prompted studies of inhibiting telomerase with the HIV RT inhibitor azidothymidine (AZT). Previously, we have demonstrated that AZT binds preferentially to telomeres, inhibits telomerase and enhances tumor cell senescence, and apoptosis after AZT treatment in breast mammary adenocarcinoma cells. Since then, several studies have considered AZT for telomerase inhibition and have led to potential clinical strategies for anticancer therapy. This review covers present thinking of the inhibition of telomerase by AZT and future treatment protocols using the drug.
端粒酶是一种高度专业化的逆转录酶（RT），端粒长度的维持取决于这种特殊的酶。人类端粒酶全酶是一种由催化亚基 hTERT、RNA 成分 hTR 和一组相关蛋白组成的核糖核蛋白。端粒酶通常在胚胎细胞中表达，并在成年期受到抑制。该酶在大约 85%的实体瘤中重新表达。这一观察结果使其成为开发药物的潜在靶点，这些药物可以用于治疗目的。hTERT 被鉴定为具有功能催化 RT，促使人们研究使用 HIV RT 抑制剂齐多夫定（AZT）抑制端粒酶。此前，我们已经证明 AZT 优先结合端粒，抑制端粒酶，并在乳腺癌腺癌细胞中 AZT 治疗后增强肿瘤细胞衰老和凋亡。此后，许多研究都考虑使用 AZT 抑制端粒酶，并提出了潜在的抗癌治疗临床策略。本综述涵盖了 AZT 抑制端粒酶的最新思路和未来的治疗方案。
