Abstract：
:Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs--but not either treatment alone--resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Lee C,Raffaghello L,Brandhorst S,Safdie FM,Bianchi G,Martin-Montalvo A,Pistoia V,Wei M,Hwang S,Merlino A,Emionite L,de Cabo R,Longo VDdoi
10.1126/scitranslmed.3003293subject
Has Abstractpub_date
2012-03-07 00:00:00pages
124ra27issue
124eissn
1946-6234issn
1946-6242pii
scitranslmed.3003293journal_volume
4pub_type
杂志文章abstract：:A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heteroto...
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