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E-GEOD-28556 - Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

Released on 21 March 2012, last updated on 26 June 2012
Mus musculus
Samples (24)
Array (1)
Protocols (18)
Short-term starvation (STS or fasting) provides protection to normal cells, mice, and possibly patients from a variety of chemotherapy drugs, but the possibility that it may also protect tumor cells renders its translational potential uncertain. Here we show that fasting cycles can be as effective as toxic chemotherapy drugs, and increase chemotherapy efficacy in the treatment of melanoma, glioma, breast cancer, and neuroblastoma. In vitro, STS sensitizes to chemotherapy 15 of the 17 cancer cell lines tested. In combination with chemotherapy STS results in a synergistic 20-fold increase in DNA damage, increased phosphorylation of pro-aging genes AKT and S6 kinase, reduced expression of stress resistance transcription factors FOXO3a and NFkB, elevated superoxide, and activated caspase-3; all changes not observed in normal tissues. Several of these effects are linked to the activity of heme oxygenase 1 (HO-1), whose modulation was sufficient to regulate chemotherapy-dependent cell death in breast cancer cells. These studies suggest that multiple fasting cycles have the potential to replace certain toxic chemotherapy drugs and to sensitize a wide range of tumors to chemotherapy. To obtain an unbiased view of the gene expression changes occurring in cancer cells in response to fasting, we performed genome-wide microarray analyses, using Illumina's Sentrix MouseRef-8 v2 Expression BeadChips (Illumina, San Diego, CA), on the subcutaneous 4T1 breast cancer tumor mass, heart, muscle and liver tissues from balb-c mice that were either fasted for 48 hours or fed an ad lib diet. Three mice from each of the starvation and the ad lib fed groups were used for the array studies.
Experiment type
transcription profiling by array 
Kevin G Becker <>, Alejandro Martin-Montalvo, Annalisa Merlino, Changhan Lee, Fernando M Safdie, Giovanna Bianchi, Laura Emionite, Lizzia Raffaghello, Min Wei, Rafael de Cabo, Saewon Hwang, Sebastian Brandhorst, Valter D Longo, Vito Pistoia
Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. 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 VD. , PMID:22323820
Investigation descriptionE-GEOD-28556.idf.txt
Sample and data relationshipE-GEOD-28556.sdrf.txt
Processed data (1)
Additional data (1)
Array designA-MEXP-1174.adf.txt