Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal experimental study without human subjects.
PubMed 18378900 · doi:10.1073/pnas.0708100105
What was done
Researchers tested whether short-term starvation confers differential stress resistance against oxidative stress and chemotherapy across three models: S. cerevisiae (wild-type, proto-oncogene mutants, or expressing oncogenic Ras2(val19)); primary glial cells alongside six rat and human glioma and neuroblastoma cell lines exposed to hydrogen peroxide or cyclophosphamide under low-glucose or low-serum conditions; and mice bearing injected neuroblastoma tumors treated with high-dose etoposide following short-term fasting.
What was found
Short-term starved yeast or mutants lacking proto-oncogene homologs showed up to 1,000-fold greater protection against oxidative stress or chemotherapy drugs compared to Ras2(val19)-expressing cells. Low-glucose or low-serum media protected primary glial cells but failed to protect any of the six malignant cell lines against hydrogen peroxide or cyclophosphamide. In vivo, short-term starvation provided complete protection to mice against high-dose etoposide without protecting injected neuroblastoma cells. Exact animal sample sizes and quantitative survival rates were not reported in the abstract.
Why it matters
This study established the preclinical concept of starvation-dependent differential stress resistance, suggesting fasting could selectively shield healthy host tissues from cytotoxic chemotherapy without reducing tumor vulnerability.
Limits
The study is entirely preclinical, using yeast, cultured cell lines, and mice, so findings cannot directly establish clinical safety or efficacy in humans. Specific animal sample sizes, fasting durations, chemotherapy dosages, tumor burden metrics, and confidence intervals were omitted from the abstract.
Cited by
- supports In a fasted ketogenic state, healthy cells slow division and boost defenses while cancer cells continue dividing rapidly, causing healthy cells to survive chemotherapy better than cancer cells.