A Glycosylated Nitric Oxide Donor, β-Gal-NONOate, and its Site-specific Antitumor Activity
✍ Scribed by Chang Chen; Yanqiu Shi; Song Li; Qingsheng Qi; Li Gu; Jing Song; Peng George Wang
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 903 KB
- Volume
- 339
- Category
- Article
- ISSN
- 0365-6233
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
So far, nitric oxide (NO) donors have been applied to various aspects of antitumor therapy. To selectively sensitize tumor cells and avoid unwanted side effects, we recently synthesized a β‐galactosidase‐activatable NO‐releasing compound, β‐galactosyl‐pyrrolidinyl diazeniumdiolate (β‐Gal‐NONOate). In this study, we first verified its superiority over its parent diazeniumdiolate (NONOate) in terms of targeted intracellular NO‐releasing and antitumor activity with 9L/LacZ cells (rat glioma cell line 9L with transformed LacZ gene) in vitro. β‐Gal‐NONOate only released NO when hydrolyzed by induced β‐galactosidase in 9L/LacZ cells, which led to its more powerful cytotoxicity than that of NONOate. The results showed that β‐Gal‐NONOate produced higher NO levels than NONOate in 9L/LacZ cells at equal concentration, and hence induced optimal NO levels for antitumor activity. However, in 9L cells, β‐Gal‐NONOate showed less toxicity than NONOate. Therefore, it is demonstrated that β‐Gal‐NONOate is a site‐specific prodrug for targeting NO intracellularly as a β‐galactosidase‐sensitive NO donor, and it is also expected to be a promising probe in numerous experimental settings and a potential therapeutic drug for antitumor treatment.