Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.
Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.
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发表时间：
1999-02
期刊：
影响因子：
11.2
通讯作者：
E. Izbicka;R. Wheelhouse;R. Wheelhouse;E. Raymond;K. Davidson;R. Lawrence;Daekyu Sun;B. Windle
中科院分区：
文献类型：
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作者：
E. Izbicka;R. Wheelhouse;R. Wheelhouse;E. Raymond;K. Davidson;R. Lawrence;Daekyu Sun;B. Windle
一系列阳离子卟啉已被鉴定为 G-四链体相互作用剂 (QIA)，可稳定端粒 G-四链体 DNA，从而抑制人端粒酶；当卟啉浓度在 50 µM 范围内时，HeLa 无细胞提取物可实现 50% 的端粒酶活性抑制。卟啉很容易被培养的肿瘤细胞核吸收。亚细胞毒性浓度的 TMPyP4 对 MCF7 细胞中端粒酶活性的抑制在 1-100 microM TMPyP4 培养 15 天（10 倍群体倍增时间）中显示出时间和浓度依赖性。端粒酶活性的抑制与 G2-M 细胞生长停滞同时发生。这些结果表明，卟啉的相关生物效应可以在对细胞不具有一般细胞毒性作用的浓度下实现。此外，数据支持这样的概念：合理的、基于结构的方法可以设计新型端粒相互作用剂，并应用于选择性和特异性抗癌治疗。
A series of cationic porphyrins has been identified as G-quadruplex interactive agents (QIAs) that stabilize telomeric G-quadruplex DNA and thereby inhibit human telomerase; 50% inhibition of telomerase activity was achieved in HeLa cell-free extract at porphyrin concentrations in the range 50 microM. The porphyrins were readily absorbed into tumor cell nuclei in culture. Inhibition of telomerase activity in MCF7 cells by subcytotoxic concentrations of TMPyP4 showed time and concentration dependence at 1-100 microM TMPyP4 over 15 days in culture (10 population doubling times). The inhibition of telomerase activity was paralleled by a cell growth arrest in G2-M. These results suggest that relevant biological effects of porphyrins can be achieved at concentrations that do not have general cytotoxic effects on cells. Moreover, the data support the concept that a rational, structure-based approach is possible to design novel telomere-interactive agents with application to a selective and specific anticancer therapy.