Antitumor activity of a polypyridyl chelating ligand: in vitro and in vivo inhibition of glioma.
Antitumor activity of a polypyridyl chelating ligand: in vitro and in vivo inhibition of glioma.
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DOI：
10.1177/1759091415572365
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发表时间：
2015-01
期刊：
影响因子：
4.7
通讯作者：
Wilson EH
中科院分区：
文献类型：
--
作者：
David CN;Frias ES;Elix CC;McGovern KE;Walker AM;Eichler JF;Wilson EH
多形性胶质母细胞瘤是一种极具侵袭性和侵袭性的中枢神经系统肿瘤，通常用化疗药物替莫唑胺治疗。不幸的是，即使经过治疗，中位生存时间也不到12个月。2，9-二仲丁基-1，10-菲咯啉（SBP）是一种基于菲咯啉的配体，最初开发用于输送金基抗癌药物，最近已被证明其本身具有显着的抗肿瘤活性。假设SBP通过与非DNA靶标相互作用启动肿瘤细胞死亡，并且考虑到大多数胶质母细胞瘤药物通过DNA损伤过程杀死肿瘤，SBP被测试为针对基于胶质细胞的肿瘤的潜在新型候选药物。体外研究表明，SBP显著抑制啮齿动物GL-26和C6胶质瘤细胞以及人U-87和SW 1088胶质母细胞瘤/星形细胞瘤的生长。此外，在小鼠中使用同基因胶质瘤模型，SBP的体内给药显著减小了肿瘤体积并延长了存活时间。在体外对非致瘤原代小鼠和人星形胶质细胞没有显著毒性，在从非癌小鼠获得的离体组织中观察到有限的毒性。末端脱氧核苷酸转移酶dUTP缺口末端标记染色和恢复分析表明，SBP诱导胶质瘤细胞凋亡。这项探索性研究表明，SBP可有效减缓脑中致瘤细胞的生长，同时对正常细胞和组织表现出有限的毒性，因此应进一步研究其在胶质母细胞瘤治疗中的潜力。
Glioblastoma multiforme is an extremely aggressive and invasive form of central nervous system tumor commonly treated with the chemotherapeutic drug Temozolomide. Unfortunately, even with treatment, the median survival time is less than 12 months. 2,9-Di-sec-butyl-1,10-phenanthroline (SBP), a phenanthroline-based ligand originally developed to deliver gold-based anticancer drugs, has recently been shown to have significant antitumor activity in its own right. SBP is hypothesized to initiate tumor cell death via interaction with non-DNA targets, and considering most glioblastoma drugs kill tumors through DNA damage processes, SBP was tested as a potential novel drug candidate against glial-based tumors. In vitro studies demonstrated that SBP significantly inhibited the growth of rodent GL-26 and C6 glioma cells, as well as human U-87, and SW1088 glioblastomas/astrocytomas. Furthermore, using a syngeneic glioma model in mice, in vivo administration of SBP significantly reduced tumor volume and increased survival time. There was no significant toxicity toward nontumorigenic primary murine and human astrocytes in vitro, and limited toxicity was observed in ex vivo tissues obtained from noncancerous mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and recovery assays suggest that SBP induces apoptosis in gliomas. This exploratory study suggests SBP is effective in slowing the growth of tumorigenic cells in the brain while exhibiting limited toxicity to normal cells and tissues and should therefore be further investigated for its potential in glioblastoma treatment.
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影响因子：
3.9
作者：
Bieda, Ruth;Ott, Ingo;Sheldrick, William S.
通讯作者：
Sheldrick, William S.
影响因子：
2.9
作者：
David, Clement;Nance, J. Philip;Wilson, Emma H.
通讯作者：
Wilson, Emma H.
影响因子：
4.1
作者：
Duffau, Hugues
通讯作者：
Duffau, Hugues
影响因子：
158.5
作者：
Hegi, ME;Diserens, A;Stupp, R
通讯作者：
Stupp, R
影响因子：
7.2
作者：
DANAN, G;BENICHOU, C
通讯作者：
BENICHOU, C