Vedenkin Alexander S, Stovbun Sergey V, Bukhvostov Alexander A, Zlenko Dmitry V, Stovbun Ivan S, Silnikov Vladimir N, Fursov Valentin V, Kuznetsov Dmitry A
N.N. Semenov Federal Research Center for Chemical Physics RAS, Moscow, Russia.
N.I. Pirogov Russian National Research Medical University, Moscow, Russia.
Invest New Drugs. 2023 Feb;41(1):153-161. doi: 10.1007/s10637-023-01333-y. Epub 2023 Feb 7.
One of the features that differentiate cancer cells is their increased proliferation rate, which creates an opportunity for general anti-tumor therapy directed against the elevated activity of replicative apparatus in tumor cells. Besides DNA synthesis, successful genome replication requires the reparation of the newly synthesized DNA. Malfunctions in reparation can cause fatal injuries in the genome and cell death. Recently we have found that the ultra-short single-stranded deoxyribose polynucleotides of random sequence (ssDNA) effectively inhibit the catalytic activity of DNA polymerase [Formula: see text]. This effect allowed considering these substances as potential anti-tumor drugs, which was confirmed experimentally both in vitro (using cancer cell cultures) and in vivo (using cancer models in mice). According to the obtained results, ssDNA significantly suppresses cancer development and tumor growth, allowing consideration of them as novel candidates for anti-cancer drugs.
癌细胞的一个显著特征是其增殖速率增加,这为针对肿瘤细胞中复制机制活性升高的通用抗肿瘤治疗创造了机会。除了DNA合成外,成功的基因组复制还需要对新合成的DNA进行修复。修复功能的故障会导致基因组中的致命损伤和细胞死亡。最近我们发现,随机序列的超短单链脱氧核糖多核苷酸(ssDNA)能有效抑制DNA聚合酶的催化活性[公式:见原文]。这种效应使这些物质被视为潜在的抗肿瘤药物,这在体外(使用癌细胞培养物)和体内(使用小鼠癌症模型)的实验中都得到了证实。根据所得结果,ssDNA能显著抑制癌症发展和肿瘤生长,因此可将它们视为抗癌药物的新候选物。