RT Journal Article SR Electronic T1 Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy JF Science Translational Medicine FD American Association for the Advancement of Science SP 124ra27 OP 124ra27 DO 10.1126/scitranslmed.3003293 VO 4 IS 124 A1 Lee, Changhan A1 Raffaghello, Lizzia A1 Brandhorst, Sebastian A1 Safdie, Fernando M. A1 Bianchi, Giovanna A1 Martin-Montalvo, Alejandro A1 Pistoia, Vito A1 Wei, Min A1 Hwang, Saewon A1 Merlino, Annalisa A1 Emionite, Laura A1 de Cabo, Rafael A1 Longo, Valter D. YR 2012 UL http://stm.sciencemag.org/content/4/124/124ra27.abstract AB 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 RAS2val19 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.