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论文题目: Leucine deprivation inhibits proliferation and induces apoptosis of human breast cancer cells via fatty acid synthase
英文论文题目: Leucine deprivation inhibits proliferation and induces apoptosis of human breast cancer cells via fatty acid synthase
第一作者: Xiao, F; Wang, CX; Yin, HK; Yu, JJ; Chen, SH; Fang, J; Guo, FF
英文第一作者: Xiao, F; Wang, CX; Yin, HK; Yu, JJ; Chen, SH; Fang, J; Guo, FF
联系作者: Guo, FF (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Beijing, Peoples R China.
英文联系作者: Guo, FF (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Beijing, Peoples R China.
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发表年度: 2016
卷: 7
期: 39
页码: 63679-63689
摘要: 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.
英文摘要: 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.
刊物名称: ONCOTARGET
英文刊物名称: ONCOTARGET
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学科: Oncology; Cell Biology
英文学科: Oncology; Cell Biology
影响因子: 5.168
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论文类别: Article
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