title: Leucine deprivation inhibits proliferation and induces apoptosis of human breast cancer cells via fatty acid synthase.
abstract: Substantial studies on fatty acid synthase (FASN) have focused on its role in regulating lipid metabolism and researchers have a great interest in treating cancer with dietary manipulation of amino acids. In the current study, we found that leucine deprivation caused the FASN-dependent anticancer effect. Here we showed that leucine deprivation inhibited cell proliferation and induced apoptosis of MDA-MB-231 and MCF-7 breast cancer cells. In an in vivo tumor xenograft model, the leucine-free diet suppressed the growth of human breast cancer tumors and triggered widespread apoptosis of the cancer cells. Further study indicated that leucine deprivation decreased expression of lipogenic gene FASN in vitro and in vivo. Over-expression of FASN or supplementation of palmitic acid (the product of FASN action) blocked the effects of leucine deprivation on cell proliferation and apoptosis in vitro and in vivo. Moreover, leucine deprivation suppressed the FASN expression via regulating general control non-derepressible (GCN)2 and sterol regulatory element-binding protein 1C (SREBP1C). Taken together, our study represents proof of principle that anticancer effects can be obtained with strategies to deprive tumors of leucine via suppressing FASN expression, which provides important insights in prevention of breast cancer via metabolic intervention.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Fei
authors: F
authors: Xiao
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Chunxia
authors: C
authors: Wang
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Hongkun
authors: H
authors: Yin
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Junjie
authors: J
authors: Yu
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Shanghai
authors: S
authors: Chen
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Jing
authors: J
authors: Fang
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, The Graduate School of The Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors: Feifan
authors: F
authors: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D054890:Fatty Acid Synthase, Type I; D005227:Fatty Acids; D007930:Leucine; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D051780:Sterol Regulatory Element Binding Protein 1; C518729:FASN protein, human; C529271:EIF2AK4 protein, human
keywords: apoptosis; breast cancer; leucine deprivation; proliferation