Glutathione-Depleting Pro-Oxidant as a Selective Anticancer Therapeutic Agent
| العنوان: | Glutathione-Depleting Pro-Oxidant as a Selective Anticancer Therapeutic Agent |
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| المؤلفون: | Dongin Kim, Seri Hong, Donghyuck Yoo, Eunkyeong Jung, Hyejin Hyun, Joungyoun Noh, Semee Seon, Dongwon Lee |
| المصدر: | ACS Omega, Vol 4, Iss 6, Pp 10070-10077 (2019) ACS Omega |
| بيانات النشر: | American Chemical Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | lcsh:Chemistry, chemistry.chemical_compound, chemistry, lcsh:QD1-999, General Chemical Engineering, Cancer cell, Toxicity, Cancer research, macromolecular substances, General Chemistry, Glutathione, Pro-oxidant, Article |
| الوصف: | A main challenge in the development of anticancer drugs that eradicate cancer cells specifically with minimal toxicity to normal cells is to identify the cancer-specific properties. Cancer cells sustain a higher level of reactive oxygen species, owing to metabolic and signaling aberrations and unrestrained growth. Cancer cells are also furnished with a powerful reducing environment, owing to the overproduction of antioxidants such as glutathione (GSH). Therefore, the altered redox balance is probably the most prevailing property of cancer cells distinct from normal cells, which could serve as a plausible therapeutic target. In this work, we developed a GSH-depleting pro-oxidant, benzoyloxy dibenzyl carbonate, termed B2C, which is capable of rapidly declining GSH and elevating oxidative stress to a threshold level above which cancer cells cannot survive. B2C was designed to release quinone methide (QM) that rapidly depletes GSH through esterase-mediated hydrolysis. B2C was able to rapidly deplete GSH and induce an overwhelming level of oxidative stress in cancer cells, leading to mitochondrial disruption, activation of procaspase-3 and PARP-1, and cleavage of Bcl-2. In the study of tumor xenograft models, intravenously injected B2C caused apoptotic cell death in tumors and significantly suppressed tumor growth. These findings provide a new insight into the design of more effective anticancer drugs, which exploit altered redox balance in cancer cells. |
| اللغة: | English |
| تدمد: | 2470-1343 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d35aaffcfec95755e6b3ac83b8335440 https://doaj.org/article/74dd33eeac1640029d3c894bd1ec2e24 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d35aaffcfec95755e6b3ac83b8335440 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 24701343 |
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