Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

Lizzia Raffaghello, Changhan Lee, Fernando M. Safdie, Min Wei, Federica Madia, Giovanna Bianchi, Valter D. Longo

Research output: Contribution to journalArticlepeer-review


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 cells but not six different rat and human glioma and neuroblastoma 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/prooxidant 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.

Original languageEnglish
Pages (from-to)8215-8220
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
Publication statusPublished - Jun 17 2008


  • Maintenance mode
  • Reactive oxygen species
  • Short-term starvation

ASJC Scopus subject areas

  • Genetics
  • General


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