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.