期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 24, 页码 8215-8220出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0708100105
关键词
reactive oxygen species; short-term starvation; maintenance mode
资金
- NIA NIH HHS [R01 AG025135, R01 AG020642, AG025135, AG20642] Funding Source: Medline
Strategies to treat cancer have focused primarily on the killing of tumor cells. Here, we describe a differential stress resistance (DSR) method that focuses instead on protecting the organism but not cancer cells against chemotherapy. Short-term starved S. cerevisiae or cells lacking proto-oncogene homologs were up to 1,000 times better protected against oxidative stress or chemotherapy drugs than cells expressing the oncogene homolog Ras2(val19). Low-glucose or low-serum media also protected primary glial calls but not six different rat and human glioma and neuroblastorna cancer cell lines against hydrogen peroxide or the chemotherapy drug/pro-oxidant cyclophosphamide. finally, short-term starvation provided complete protection to mice but not to injected neuroblastoma cells against a high dose of the chemotherapy drug/pro-oxidant etoposide. These studies describe a starvation-based DSR strategy to enhance the efficacy of chemotherapy and suggest that specific agents among those that promote oxidative stress and DNA damage have the potential to maximize the differential toxicity to normal and cancer cells.
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