期刊
EXPERIMENTAL GERONTOLOGY
卷 48, 期 10, 页码 1120-1128出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2013.02.016
关键词
Calorie restriction; Protein restriction; Fasting; Macronutrients; Stress resistance; Tumor progression; Insulin-like growth factor 1; Chemotherapy
资金
- NIH
- NIA [AG20642, AG025135, AG034906]
- Bakewell Foundation
- V Foundation for Cancer Research, a USC Norris Cancer Center pilot grant
- NCI [HHSN261201000098C]
Short-term starvation (STS) protects normal cells while simultaneously sensitizing malignant cells to high-dose chemotherapeutic drugs in mice and possibly patients. The fasting-dependent protection of normal cells and sensitization of malignant cells depends, in part, on reduced levels of insulin-like growth factor-1 (IGF-1) and glucose. Calorie restricted diets with defined macronutrient (carbohydrate, protein, fat) ratios were evaluated for the effects on stress sensitization markers and protection in mice treated with high-dose chemotherapy. We show that short-term CR significantly reduced both glucose and IGF-1 levels, but when specific macronutrient deficiencies were tested, only the complete lack of proteins reduced IGF-1 levels. Short-term 50% CR combined with either severe protein-deficiency or ketogenic diets improved chemotoxicity resistance similarly to the standard 50% CR, but did not result in the high protection caused by STS. Notably, a high protein diet reversed the beneficial effects of short-term CR. In a subcutaneous mouse model of glioma, feeding a low protein (4% calories from protein) diet for more than 20 days did not delay tumor progression once the tumor became palpable. Also, cycles of short-term (3 days) 50% CR did not augment the chemotherapy efficacy of cisplatin in a murine breast cancer model. These results indicate that the protection from chemotoxicity and retardation of the progression of certain tumors achieved with fasting is not obtained with short-term calorie and/or macronutrient restriction. (C) 2013 Elsevier Inc. All rights reserved.
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