Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing

被引:29
作者
Barak, Yoram [1 ,6 ]
Schreiber, Frank [2 ]
Thorne, Steve H. [3 ,4 ,5 ]
Contag, Christopher H. [3 ,4 ]
deBeer, Dirk [2 ]
Matin, A. [1 ]
机构
[1] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
[2] Max Planck Inst Marine Microbiol, Microsensor Res Grp, D-28359 Bremen, Germany
[3] Stanford Univ, Dept Pediat, Sch Med, James H Clark Ctr, Stanford, CA 94305 USA
[4] Stanford Univ, Bio X Program, Sch Med, James H Clark Ctr, Stanford, CA 94305 USA
[5] Univ Pittsburgh, Dept Surg Oncol, Hillman Canc Ctr, Pittsburgh, PA 15232 USA
[6] Codexis Inc, Redwood City, CA 94063 USA
来源
BMC CANCER | 2010年 / 10卷
关键词
DONATING ASPIRIN; THERAPY; CHEMOTHERAPY; INDUCTION; APOPTOSIS; BACTERIA; STRESS; ENZYME; TUMORS;
D O I
10.1186/1471-2407-10-146
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it. Methods: Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro) or using Biosensors (in vivo). Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques. Results: SL7838 generated nitric oxide (NO) in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp-and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838. Conclusions: NO generation capability is important in the killing of cancer cells by Salmonella strains.
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页数:6
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